Exploring the applicability, combined strategies, and challenges of ablation in hematology based on its characteristics and immunomodulatory mechanisms.

Introduction

Malignant hematological diseases are a group of malignancies originating from the hematopoietic and lymphoid systems, encompassing multiple subtypes such as lymphoma, leukemia, and multiple myeloma. Characterized by high incidence, strong biological heterogeneity, and complex clinical manifestations, they pose a serious threat to global public health [ 1 , 2 ]. Over the past few decades, the treatment paradigm for malignant hematological diseases has gradually formed a system centered on systemic therapies including chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and targeted therapy. These treatments have significantly improved the survival outcomes of some patients, but still face prominent challenges in clinical practice [ 3 , 4 ].

For locally progressive lesions such as large lymphoma masses and extramedullary myeloma nodules, systemic therapy often fails to achieve sufficient local efficacy, resulting in persistent tumor burden and even compression of surrounding vital organs (e.g., spinal cord, orbit, abdominal organs), which seriously impairs patients’ quality of life [ 5 ]. Relapsed/refractory hematological diseases are often accompanied by tumor cell drug resistance; repeated systemic therapy not only increases cumulative toxicity but also further impairs patients’ immune function, leading to poor prognosis [ 6 ]. In addition, special populations such as the elderly, frail patients, and those with comorbid organ dysfunction are often unable to tolerate high-intensity standard treatment [ 7 ], and there is an urgent need for safe and effective alternative therapies.

With the in-depth development of precision medicine, minimally invasive ablation technology has emerged as a research hotspot in the field of oncology. By utilizing physical energy such as thermal energy, cryogenic energy, and electrical energy to directly ablate tumor tissue [ 8 – 10 ], this technology achieves therapeutic goals without extensive surgical resection. It possesses core advantages including minimal trauma, rapid postoperative recovery, and strong targeting, and has been widely used in the treatment of solid tumors such as liver cancer, lung cancer, and thyroid cancer, demonstrating definite efficacy [ 11 – 13 ]. However, compared with its mature application in solid tumors, research on ablation technology in hematological diseases is still in the exploratory stage. Literature searches show that existing related studies are mostly small-sample, single-center case reports or retrospective analyses, lacking large-sample randomized controlled trials (RCTs) to verify its long-term efficacy and safety [ 14 , 15 ]. Furthermore, issues such as the optimization of ablation parameters and protocols based on the unique biological characteristics of hematological lesions (e.g., diffuse infiltration, sensitivity to microenvironmental changes, and rich blood supply), the systematic elucidation of immunomodulatory mechanisms, and the development of standardized operating procedures for lesions in special sites have not been fully resolved.

Addressing the aforementioned research gaps, this review systematically summarizes the current application status of three mainstream ablation technologies—radiofrequency ablation, microwave ablation, and cryoablation—in hematological diseases. It focuses on analyzing the technical characteristics, mechanisms of action, clinical application scenarios, indications, and contraindications of each ablation technology, and deeply discusses the current challenges and future development directions. The aim is to integrate existing research findings, clarify the application value and potential of ablation technology in hematological diseases, and provide comprehensive references for clinical practitioners in hematology to carry out minimally invasive local treatment and promote the in-depth development of related research.

This study conducted a systematic search in PubMed and Web of Science databases (primary time range: January 2000 to December 2025), using Boolean logic search terms related to ‘ablation’, ‘lymphoma’, ‘multiple myeloma’, and ‘extramedullary lesions’ for preliminary screening. The inclusion criteria for literature were: clinical studies, case reports, and mechanistic research involving the application of ablation techniques in hematologic malignancies. Exclusion criteria primarily included non-English language articles and conference abstracts. The final studies for analysis underwent independent screening by two reviewers, with particular emphasis on literature targeting hematologic conditions such as lymphoma and extramedullary lesions of myeloma.

Mainstream ablation technologies: mechanisms, progress, and application scenarios in hematological diseases

Due to its core advantages of precise targeting, minimal trauma, and strong controllability, ablation technology has been widely used in the treatment of solid tumors. Targeting the biological characteristics of hematological lesions (e.g., lymphoma masses, extramedullary myeloma lesions) such as diffuse infiltration, sensitivity to microenvironmental changes, and frequent infiltration of special sites, three mainstream ablation technologies—radiofrequency ablation, microwave ablation, and cryoablation—have demonstrated unique adaptive value after optimization. This section systematically sorts out their core mechanisms and technical progress, and focuses on their application directions in hematological disease scenarios.

Radiofrequency ablation (RFA)

Core mechanism of action

Radiofrequency ablation relies on high-frequency alternating current (400–500 kHz) to act on lesion tissue through electrodes, causing intense vibration and friction of intracellular ions to generate heat (Fig. 1 ). The local temperature is raised to 60–100 °C, leading to tumor cell protein denaturation, loss of enzyme activity, and DNA damage, ultimately forming coagulative necrosis [ 8 ]. The propagation of its thermal effect depends on tissue conductivity, which is significantly influenced by the water content of the lesion, blood supply status, and electrode position: when the temperature exceeds 60 °C, tumor cells undergo irreversible damage within seconds; when the temperature rises to 90–100 °C, the tissue is rapidly vaporized to form a “carbonized zone”, which on the contrary reduces heat conduction efficiency and limits the ablation range [ 16 ].

In addition to the direct tumor-killing effect, radiofrequency ablation can activate anti-tumor immune responses by inducing immunogenic cell death (ICD). Studies have confirmed that tumor cell necrosis caused by ablation releases damage-associated molecular patterns (DAMPs) such as calreticulin (CRT) and high-mobility group box 1 (HMGB1), recruits antigen-presenting cells such as dendritic cells (DCs), and promotes tumor antigen cross-presentation and CD8 + cytotoxic T cell activation [ 17 ].

Key technological progress and adaptive scenarios in hematological diseases

Optimization of electrode design is the core direction of RFA technology development [ 18 ]. Early monopolar electrodes had a limited ablation range (usually < 3 cm in diameter) [ 19 ] and were susceptible to the “heat sink effect”—blood flow adjacent to large blood vessels carries away heat, leading to residual tumor at the lesion edge [ 20 ]. In contrast, multipolar umbrella-shaped electrodes can achieve more uniform necrosis and a higher pathological complete necrosis rate [ 21 ]; cooled-cycle electrodes reduce the temperature of tissue around the electrode through internal circulating cooling water, minimizing carbonization, improving heat conduction efficiency, and reducing the risk of skin burns [ 22 ]. Currently, there are few clinical studies on RFA in hematological diseases. However, based on its technical characteristics (uniform necrosis achievable with multipolar electrodes and reduced carbonization with cooled-cycle electrodes) and treatment experience in lymph node metastases of solid tumors [ 23 ], it is speculated to be suitable for medium-sized lymphoma masses (3–5 cm in diameter) and superficial lymph node infiltration lesions.

Advancements in image-guided technology have significantly improved the accuracy of RFA. Ultrasound has become the preferred guidance method due to its real-time performance and lack of radiation [ 24 ], suitable for superficial hematological lesions such as those in the neck and armpits; for deep lesions in the lungs, liver (e.g., distant metastatic nodules of lymphoma), CT guidance can clearly show the anatomical relationship between the lesion and blood vessels [ 25 ], reducing the risk of bleeding.

Microwave ablation (MWA)

Core mechanism of action

The microwave antenna for MWA has a length of 15 to 30 centimeters and a needle gauge of 14 to 20. The generator and antenna are connected by a flexible coaxial cable, which can be internally cooled (Fig. 2 ) [ 26 ]. Microwave ablation utilizes microwave electromagnetic fields to make polar molecules (mainly water molecules) in the lesion tissue rotate and vibrate at high speed to generate heat, rapidly raising the local temperature to 100–150 °C to achieve thermal coagulative necrosis of tumor tissue [ 9 ]. Compared with RFA, its unique advantages are more suitable for the treatment needs of hematological diseases: first, higher heating efficiency, which can reach the effective killing temperature within minutes, significantly shortening the treatment time and reducing the tolerance pressure on patients [ 9 ], especially suitable for elderly and frail hematological patients; second, heat conduction is not affected by tissue conductivity and is slightly interfered by the “heat sink effect” [ 8 ], resulting in more stable therapeutic effects for hypervascular lymphoma lesions or perivascular invasive lesions.

The immunomodulatory effect of MWA is more significant. High temperature can release tumor antigens more fully, while upregulating the expression of co-stimulatory molecules such as CD80 and CD86 on the surface of dendritic cells to promote their maturation and differentiation. In tumor models, MWA can significantly increase the proportion of CD4 + effector memory T cells and the cytotoxicity of CD8 + T cells in peripheral blood. This enhanced immune response is of great significance for eliminating minimal residual lesions of hematological diseases and reducing the risk of recurrence. It should be noted that incomplete microwave ablation (iMWA) may induce an inhibitory tumor microenvironment (TME). iMWA can promote the chemokine CXCL5, leading to a decrease in CD4 + T cells, CD8 + T cells, natural killer (NK) cells, and macrophages (including M1 and M2 types), but an increase in monocytes and myeloid-derived suppressor cells (MDSCs), which instead accelerates tumor progression [ 27 ].

Key technological progress and application in hematological diseases

Innovation in antenna design is the core of MWA technological development. Coaxial monopolar antennas have a simple structure but carry the risk of energy leakage; dual-slot antennas achieve concentrated energy release by optimizing the radiation slot structure, with a low reflection coefficient [ 28 ]; water-cooled microwave antennas cool the antenna rod through internal circulating cooling water, effectively reducing blood loss at the ablation Sect [ 29 ]. ; multi-antenna synergistic ablation technology can obtain a larger ablation area by precisely controlling the antenna spacing (usually 1–2 cm) and energy distribution. Both dual-slot antennas, water-cooled microwave antennas, and multi-antenna synergy can achieve a more spherical ablation area compared with coaxial monopolar antennas [ 28 , 30 , 31 ].

In adaptive scenarios for hematological diseases, ultrasound-guided MWA has been applied in parotid gland adenolymphoma and Mycosis fungoides [ 32 , 33 ]. Compared with traditional surgical methods, MWA has less trauma, faster recovery, and fewer side effects. As a palliative treatment, it can greatly relieve patients’ clinical symptoms and improve their quality of life.

Cryoablation (CA)

Core mechanism of action

Based on the Joule-Thomson effect, cryoablation achieves tumor tissue cooling (to below − 40 °C) through the rapid expansion of high-pressure argon, followed by rewarming with helium to form a “freeze-thaw cycle” for tumor killing (Fig. 3 ) [ 10 ]. Its mechanisms of action include four aspects: first, the formation of intracellular ice crystals leading to cell membrane rupture and organelle damage; second, microvascular embolism—freezing causes vascular endothelial damage and platelet aggregation, forming thrombi to block tumor blood supply, resulting in ischemic necrosis; third, changes in osmotic pressure—the formation of extracellular ice crystals induces cell dehydration and electrolyte disturbance, further exacerbating cell death; fourth, immunomodulatory effect—tumor antigens released by cryogenic necrosis can activate the body’s “cryoimmunity” response and enhance anti-tumor immune reactions [ 34 , 35 ].

Key technological progress and application in hematological diseases

Compared with thermal ablation, the unique advantages of cryoablation make it more suitable for specific hematological scenarios: it can temporarily inactivate nerve endings during treatment, having a good analgesic effect [ 36 , 37 ], especially suitable for lesions with severe pain such as myeloma bone infiltration and lymphoma bone metastasis; the ablation boundary of cryoablation is clear, and the formation process of the “ice ball” can be intuitively observed through imaging, facilitating precise control of the ablation range and avoiding excessive damage to normal tissue [ 15 ].

Although argon and helium are widely used to cool cryoprobes, the availability and cost of rare gases are relatively challenging for low- and middle-income countries [ 38 ]. To address this issue, a more cost-effective carbon dioxide-based cryoablation device has been developed [ 39 ]. High-pressure carbon dioxide gas can expand and cool to as low as -78.5 °C, creating an environment suitable for ice formation and cell necrosis [ 40 ]. In the field of hepatocellular carcinoma, a study involving 427 patients with unresectable HCC showed that transcatheter arterial chemoembolization (TACE) before cryosurgery can improve the efficacy of cryoablation and reduce adverse reactions, especially bleeding. For unresectable hepatocellular carcinoma, especially large hepatocellular carcinoma, sequential TACE followed by cryosurgery is a promising combined treatment regimen [ 41 ].

Existing studies have shown that cryoablation can be used as a novel therapeutic strategy for local tumor control in B-cell malignancies. Our team was the first to demonstrate the good safety and efficacy of combined ablation and chemotherapy in elderly and frail patients with extramedullary myeloma lesions and large extramedullary masses of diffuse large B-cell lymphoma [ 15 ]. As we all know, bridging therapy before Chimeric Antigen Receptor T-Cell (CAR-T cell) infusion is very necessary. A study by Zhang et al. first proved that cryoablation can be used as a novel bridging treatment before CAR-T cell therapy to quickly achieve local tumor control and reduce tumor burden [ 42 ].

Comparison of characteristics of three ablation technologies

Mechanisms of ablation

Direct tumor killing effect

Thermal ablation directly causes cell necrosis through protein denaturation and cell membrane rupture; cryoablation induces ischemic necrosis through ice crystal formation leading to cell dehydration, organelle damage, and intravascular thrombosis [ 43 ].

Abscopal effect and immune regulation

There is a complex dynamic interaction between the immune system and cancer. Cancer can manipulate the immune system through various mechanisms to support its own proliferation, and cancer treatment can in turn regulate the immune response. Unlike traditional chemotherapy or surgery, local ablation can generate strong anti-tumor immunity by stimulating adaptive and innate immune responses, thereby not only killing the local tumor, but also destroying tumor cells in other lesions through the abscopal effect.

Tumor antigens

In addition to directly killing tumor cells through physical destruction, local treatments such as radiotherapy [ 44 – 46 ], ablation [ 47 , 48 ], and even hyperthermia [ 49 ] can directly or indirectly induce cell death, thereby exposing cell contents containing tumor antigens to the extracellular space [ 50 ]. These antigenic substances enter the local lymphatic drainage and are recognized as antigens by T cells or B cells [ 51 ], thereby activating CD8 + CTL response and cellular tumor immunity [ 52 ], triggering immunogenic cell death (ICD). However, generally speaking, the post-ablation immunogenicity induced by cryoablation is higher than that of thermal ablation [ 53 , 54 ]. This is because thermal ablation mainly causes protein denaturation, resulting in less exposure of tumor antigen proteins to the immune system and reduced antigenicity of proteins [ 55 ]. In contrast, cryogenic methods generally preserve protein structures, so their immunogenicity is stronger, the abscopal effect is more obvious [ 56 ], and the risk of systemic inflammatory response syndrome is also higher [ 57 ].

Immunogenic cell death (ICD)

ICD is a cell death mode that activates innate immune cells (including antigen-presenting cells) by molecular signals, mainly mediating the activation of adaptive anti-tumor immunity through the release of damage-associated molecular patterns (DAMPs) [ 58 ]. During ablation, DAMPs are released from tumor cells, stromal cells, endothelial cells, immune cells, and damaged extracellular matrix [ 59 ], inducing innate immune cells to produce inflammatory factors such as TNF, IL-1, IL-6, and IL-8 [ 50 , 60 ], while recruiting and regulating immune cells such as neutrophils, macrophages, and dendritic cells (DCs), and ultimately activating anti-tumor immunity [ 50 ]. It should be noted that uninduced tumor cell death (such as death caused by hypoxia) usually has no immunostimulatory effect due to the lack of DAMPs release.

Within hours to days after thermal ablation, the levels of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-18, TNF-α) increase [ 61 ], while anti-inflammatory factors (IL-10, TGF-β) are also released. Cryoablation releases similar types of cytokines but in different quantities. For example, the release of nuclear factor-κB-dependent cytokines (IL-1, IL-6, TNF-α) is higher than that of radiofrequency and microwave ablation [ 62 ], which may trigger systemic inflammatory response syndrome (SIRS), namely “cryoshock”. In severe cases, it can lead to disseminated intravascular coagulation, multiple organ failure, and even death, while thermal ablation usually does not induce SIRS [ 63 ].

Recruitment of immune effector cells and regulation of immune suppressor cells

After ablation, injury response, inflammation, and wound healing will recruit a variety of immune cells. Tumor-infiltrating lymphocytes (TILs) including cytotoxic T cells (CD8+), helper T cells (CD4+), B cells, and NK cells are gradually becoming significant biomarkers for predicting treatment effect and prognosis [ 64 ].

Immune suppressor cells in the tumor microenvironment such as cancer-associated fibroblasts, myeloid-derived suppressor cells (MDSCs), Treg, and TAM can promote tumor growth. Both thermal and cryoablation can reduce the infiltration of these cells, destroy tissue barriers, promote CTLs tumor infiltration, and enhance immune memory [ 65 , 66 ].

Maintenance of immune memory

Tissue-resident memory T cells (TRM), as a subset of CD8⁺T cells, are non-circulating and localized in tissues, playing a protective role in preventing tumor recurrence. CD8⁺TRM is associated with improved prognosis of cancer immune response (such as the long-term protective effect of skin TRM). Memory and memory-like NK cells also have immune memory characteristics against pathogens and malignant tumors. Ablation can prevent tumor recurrence by activating TRM [ 49 ].

Altering neutrophil-related inflammatory state to promote Anti-Tumor effect

Neutrophils are roughly divided into N1 and N2 types according to their different effects on immunotherapy response. Studies have shown that N1 neutrophils are often accompanied by increased infiltration levels of CD8 + T cells and NK cells, thereby enhancing anti-tumor immune response. In contrast, high infiltration of N2 neutrophils is a key factor leading to dysfunction of NK cells or CD8 + T cells. It has been observed in cryoablation [ 56 ] that it can change the phenotype of neutrophils to promote anti-tumor effect. Figure 4 illustrates the mechanisms of cold ablation and thermal ablation.

Current status and countermeasures of local treatment for hematological diseases

Clinical application scenarios

Currently, the treatment of malignant hematologic diseases is still predominantly systemic therapy, which exhibits significant limitations in scenarios such as local progression, refractory relapse, and poor tolerance in special populations. As a minimally invasive local treatment modality, ablation technology can specifically address the following clinical issues:

Reducing tumor burden and improving sensitivity to systemic therapy

For residual solitary lesions or large masses after chemotherapy, local ablation can achieve radical cure, or eliminate drug-resistant cell clones and reduce tumor burden, creating conditions for subsequent combined chemotherapy [ 67 ] and even CAR-T cell therapy [ 42 ]. Especially for patients with organs such as the liver that cannot be cured by chemotherapy, local ablation can eliminate residual lesions [ 14 , 68 ].

Relieving symptoms and improving quality of life

Local invasion of lymphoma can cause symptoms such as pain, spinal cord compression, respiratory compression, compression of important abdominal organs [ 68 ], and even damage to other important organ functions such as the eyes [ 69 ]. Ablation can rapidly reduce the lesion volume, directly relieve compression and pain, avoid additional damage caused by traditional treatments, and significantly improve patients’ quality of life.

Improving the depth of remission in patients unable to tolerate standard treatment

Elderly patients with poor physical status or combined with multiple organ dysfunction cannot tolerate high-intensity chemotherapy. Local ablation can be used as palliative treatment to control local lesions while avoiding systemic toxicity. Deepak reported a patient with post-transplant lymphoproliferative disorder (PTLD) refractory after transplantation. The lung lesions achieved complete remission after DA-EPOCH-R chemotherapy, but the residual liver lesions achieved disease-free survival for 4 years after ablation [ 68 ].

Reducing the risk of compression, pain and paralysis caused by myeloma bone disease

70–100% of patients with multiple myeloma (MM) have cytokine-induced osteoclastic bone resorption, 55%-70% of multiple myeloma patients will have vertebral fractures, and 30% will have neurological dysfunction due to spinal cord or nerve root compression. Traditional treatments include painkillers, bisphosphonates, orthopedic braces, radiotherapy, or surgery. However, studies by Orgera et al. found that ablation and percutaneous vertebroplasty are comparable in pain relief, improvement of disability scores, stabilization of bone structure, and reduction of analgesic use, providing a minimally invasive option for treatment-resistant pain, especially suitable for bone lesions in the spine, pelvis, etc [ 70 – 73 ].

Shortening the treatment time and improving the cure rate of aspergilloma

Aspergillosis is an infection caused by the fungus Aspergillus. Many hematological patients have long-term granulocytopenia and immunocompromise, especially those receiving hematopoietic stem cell transplantation [ 74 , 75 ], which are prone to pulmonary aspergillus infection and even hematogenous dissemination involving organs. Aspergilloma carrying a 38% risk of death may cause hemoptysis, and in the absence of effective treatment, the mortality rate can be as high as 80%-90% [ 76 , 77 ]. The first-line treatment for chronic aspergilloma is antifungal therapy, with an effective rate of 50–80% [ 78 ]. In cases of antifungal resistance, surgical intervention for pulmonary aspergilloma as an adjuvant to drug therapy is the gold standard [ 79 , 80 ], but surgical intervention has a complication risk of up to 63%. Common complications include pneumothorax, respiratory failure, bleeding, infection, and arrhythmia [ 81 , 82 ]. The mortality rate of surgery is 4–33% [ 82 ]. For patients with major surgical trauma or severe comorbidities, treatment options are limited, and the protracted course of aspergilloma may lead to irreversible lung damage [ 83 ], and even affect the timing of chemotherapy or transplantation. Therefore, alternative treatments need to be found.

Indications

(1) Local control of extramedullary masses: including persistent solitary lymphadenopathy or lymphadenopathy compressing important organs that cannot be operated on after lymphoma chemotherapy; solitary bone or soft tissue plasmacytoma, ablation can be selected when radiotherapy is intolerable or the expected radiotherapy effect is poor.(2) Salvage treatment for relapsed/refractory lymphoma and myeloma: ① Solitary recurrent lesions: For patients who have previously received chemotherapy or radiotherapy, if only a single recurrent lesion (such as cervical lymph nodes, splenic nodules) occurs, ablation can be used to avoid cumulative toxicity of systemic therapy; ② Intrafield recurrence after radiotherapy: Patients with local recurrence after radiotherapy who cannot receive re-radiotherapy (such as mediastinal lesions), ablation can be used as a salvage method without increasing the risk of radiation pneumonitis; ③ Bridging therapy before CAR-T or bispecific antibodies: For patients with large masses, ablation is used to reduce tumor burden, effectively reduce the risk of tumor lysis syndrome, cytokine release syndrome, etc. With the assistance of ablation-induced immune activation mechanism, it is conducive to achieving deeper remission.(3) Palliative treatment of special site lesions: ① Lesions adjacent to important organs: Lymphoma in the orbit, vertebral body, and around the pancreas, with high risk of surgery or radiotherapy, can be treated with precise ablation; ② Multiple oligometastases: ≤ 3 limited metastases (such as solitary nodules in the liver and lung), can be treated with multi-needle combined ablation.(4) Paraosseous or paravertebral tumors that are unsuitable for or refused surgical treatment, or have poor response to radiotherapy, chemotherapy, and other treatments; tumors that cannot be surgically resected due to advanced age, underlying diseases, or anatomical location.(5) Radical treatment for patients with drug-resistant or inoperable aspergilloma infection.

Contraindications

Poor general condition or dysfunction of important organs, unable to tolerate surgical procedures

Platelet count <50×10⁹/L or combined with severe coagulation dysfunction

No safe puncture path, unable to avoid key structures such as important blood vessels and nerves

Unable to discontinue drugs affecting coagulation function (such as anticoagulants, anti-angiogenic drugs) within a short period

Lesions invading or surrounding important nerves, which may cause severe nerve damage

Vertebral tumors invading intraspinal structures, cryoablation may cause paraplegia

Tumors in the skull, hip joints, hands, feet and other parts require cautious use (special anatomical structure, prone to damage to surrounding tissues)

Presence of infection at the ablation puncture site.

Combined treatment strategies of ablation technology

Combined application of ablation and immunotherapy

Ablation therapy can create favorable conditions for immunotherapy by releasing tumor antigens and activating immune responses, while immunotherapy can enhance the abscopal effect of ablation and inhibit micrometastases. This “1 + 1>2” synergistic effect has been confirmed in multiple studies [ 84 , 85 ]. For hematological diseases, this combined model is particularly suitable for relapsed/refractory cases or patients with metastases: ablation first reduces tumor burden through local tumor reduction, reconstructs the tumor immune microenvironment, and breaks immune tolerance; subsequent immunotherapy (such as PD-1 inhibitors, CAR-T cell therapy) can accurately identify and eliminate residual tumor cells, strengthen the systemic anti-tumor immune response, and significantly reduce the risk of recurrence [ 86 , 87 ]. Currently, combined ablation and immunotherapy have shown definite efficacy in solid tumors [ 88 , 89 ], and their synergistic mechanisms and clinical value in hematological diseases urgently need to be verified by multi-center studies.

Synergistic innovation of ablation and nanomedicine

The development of nanotechnology provides a new path for the precise improvement of ablation efficacy. Nanomaterials can optimize ablation therapy through three roles—“carrier, sensitizer, and contrast agent”, providing solutions for special scenarios of hematological diseases (such as microlesions, infiltration of special sites).

Nanodrug carriers can achieve targeted drug delivery to the ablation area. For example, Nano-IFNγ/Zole (a zoledronate-mineralized nanoparticle loaded with IFNγ) can remain in the ablated area of the tumor for a long time after incomplete radiofrequency ablation, enhance immune response by regulating macrophage metabolic pathways, and reduce the poor prognosis after clinical incomplete RFA [ 90 ].

Nano energy sensitizers can improve the efficiency of ablation energy utilization and reduce damage to normal tissues. Thermosensitive liposomes (TSLs) combined with microwave ablation can accurately release drugs at local high temperatures while reducing the energy required for ablation [ 91 ]. In addition, Hou et al. constructed a non-ionic MWA sensitizer encapsulating ethyl formate (EF) and doxorubicin (DOX) in liposomes (EF-DOX-Lips), which can enhance MWA and combined therapy to combat tumor recurrence induced by incomplete MWA [ 92 ].

Nanoscale imaging contrast agents can enhance the accuracy of image guidance [ 93 ]. Yu et al. found that a new class of biosynthesized nanoscale contrast agent (PEG-GVs) may produce more stable and long-lasting contrast signals, helping them penetrate beyond blood vessels [ 94 ], providing a clearer targeting basis for ablation and solving the clinical pain point of difficult localization of minimal residual lesions.

In-depth exploration of ablation-related immune mechanisms

The immunomodulatory effect of ablation is one of its core advantages in adapting to the treatment of hematological diseases, but the relevant mechanisms have not been fully clarified yet. It is necessary to explore in depth at the molecular level to guide clinical optimization:

Clarify the law of antigen release: Systematically study the impact of different ablation technologies (such as cryoablation, microwave ablation) and different parameters (such as freezing temperature, ablation time) on the type and release amount of hematological tumor antigens, and maximize the efficiency of antigen exposure through parameter optimization;

Analyze immune cell activation pathways: Focus on the key signaling molecules of dendritic cells (DCs) maturation and T cell activation, develop targeted agonists (such as DCs maturation agonists) [ 61 ], strengthen the immune activation effect induced by ablation, and break the immunosuppressive microenvironment of hematological diseases;

Block immune escape mechanisms: In-depth identification of the core pathways of tumor immune escape after ablation (such as PD-L1 upregulation [ 95 ], regulatory T cell (Treg) infiltration [ 96 ]), and combine corresponding targeted inhibitors (such as PD-1 inhibitors, Treg clearing agents) to avoid the risk of immunosuppression caused by incomplete ablation and improve treatment durability.

Discussion

Ablation technology, as a type of local treatment with precise targeting, a minimally invasive approach, and immunomodulatory potential, provides an important supplement to the clinical management of malignant hematological diseases. It demonstrates unique value in overcoming the limitations of systemic therapy and addressing the needs of special populations. This study systematically reviews the core characteristics and mechanisms of three mainstream ablation technologies—radiofrequency ablation, microwave ablation, and cryoablation—and clarifies their indications and limitations in the field of hematological diseases.Cryoablation, benefiting from its significant analgesic effect and clear ablation boundaries, has demonstrated definite safety and efficacy in treating myeloma bone infiltration, lymphoma bone metastasis, and as a bridging therapy for CAR-T treatment. Microwave ablation, characterized by rapid heating, strong resistance to the heat sink effect, and minimal trauma, has become the preferred palliative treatment for superficial hematological lesions—such as Warthin’s tumor (parotid adenolymphoma) and mycosis fungoides—as well as for elderly and frail patients. Although radiofrequency ablation currently lacks direct clinical efficacy data, after optimization with multipolar umbrella-shaped electrodes and cooled-cycle electrodes, it shows potential for treating medium-sized lymphoma masses, extramedullary myeloma nodules, and other lesions.In clinical practice, ablation technology not only effectively reduces local tumor burden and rapidly relieves organ compression and bone pain symptoms but also offers a safe and feasible treatment option for special populations who cannot tolerate high-intensity standard therapies. Additionally, ablation provides a minimally invasive alternative treatment pathway for complications such as aspergilloma infection, significantly expanding the therapeutic options for hematological diseases.

However, the standardized application of ablation technology in the field of hematological diseases still faces multiple practical challenges. Firstly, the support of clinical evidence is insufficient. Most existing studies are small sample size, single-center case reports or retrospective analyses. There is a lack of large sample size, long-term follow-up randomized controlled trials to verify their long-term survival benefits. The appropriate technologies, parameter schemes, and efficacy evaluation criteria for different pathological subtypes of hematological diseases have not yet been unified, leading to poor standardization in clinical application. Secondly, there are inherent boundaries in technical application. Thermal ablation is still affected by the heat sink effect, and marginal residues may occur in hypervascular lymphoma lesions. Incomplete microwave ablation may contribute to an inhibitory tumor microenvironment and accelerate tumor progression. Cryoablation relies on argon and helium, which are relatively costly, limiting its popularization in resource-constrained areas. Moreover, the long-term efficacy of new carbon dioxide-based cryoablation devices requires confirmation through additional clinical data. Thirdly, the immunomodulatory effect needs to be strengthened. Although ablation can activate anti-tumor immunity by releasing tumor antigens and inducing immunogenic cell death, the complex immunosuppressive microenvironment of hematological diseases (such as regulatory T cell enrichment and myeloid-derived suppressor cell infiltration) may weaken this effect.

To address the above challenges, future efforts need to promote the high-quality advancement of ablation technology in the field of hematological diseases from three aspects.

First, in terms of clinical evidence construction, multi-center, large-sample prospective studies should be carried out. These studies aim to enable the formulation of individualized ablation protocols based on different subtypes of hematological diseases, such as diffuse large B-cell lymphoma and multiple myeloma, and lesion characteristics including size, location, and blood supply status. It is also necessary to clarify indications, optimal treatment timing, and efficacy evaluation criteria, as well as to establish a long-term follow-up database to provide high-level evidence-based medical support for the development of clinical guidelines.

Second, regarding treatment strategy optimization, it is essential to deepen research on the synergistic mechanisms between ablation and systemic therapy. Further exploration of the synergistic effects of combined approaches, such as “ablation + immunotherapy” and “ablation + nanomedicine,” should be conducted. Special attention should be paid to determining the optimal intervention timing and parameter settings of ablation in CAR-T bridging therapy. This will help improve the depth and durability of treatment through the synergy of local tumor reduction and systemic immune activation. Additionally, an in-depth analysis of the molecular mechanisms underlying ablation-induced immune responses is needed. This includes clarifying the patterns of antigen release, immune cell activation pathways, and tumor immune escape mechanisms, which will provide theoretical support for combined targeted inhibitor therapies.

Third, in terms of technology popularization and standardization, continuous optimization of the performance and operational convenience of cost-effective ablation equipment is necessary. It is important to promote the multidisciplinary team (MDT) model by integrating resources from hematology, interventional radiology, and imaging departments, and to standardize operating procedures for lesions in special sites. Efforts should also focus on improving the technical proficiency of primary medical institutions and promoting the integration of ablation technology into the multidisciplinary comprehensive treatment system for malignant hematological diseases.

Conclusion

In summary, relying on its core advantages of minimal invasiveness, precision, and immune modulation, ablation technology demonstrates unique efficacy in the local treatment of hematological diseases. With the ongoing accumulation of clinical evidence, progressive optimization of treatment strategies, and increasing adoption of the technology, ablation is expected to provide individualized and minimally invasive treatment options for more patients with hematological diseases. It is especially promising for relapsed and refractory cases and special populations, thereby further enriching the treatment landscape of hematological diseases and improving patients’ survival prognosis and quality of life.

Author contributions

Y.W. (Muyun Wu) and J.Q.F. (Jiaqi Fu) drafted the core content of the review manuscript, including the literature review framework and discussion sections. R.J.S. (Runjie Sun) and M.Y. (Manya Yu) were responsible for the acquisition and systematic analysis of relevant literature data, and organized the reference list. M.T.X. (Mengting Xia) prepared all the figures (e.g., comparative charts, literature distribution maps) and tables in the manuscript. Y.Y. (Ye Yang) and X.C. (Xing Cui), as corresponding authors, designed the overall research direction of the review, revised the manuscript critically for important intellectual content, and coordinated the communication among all authors. All authors reviewed the final version of the manuscript.

Funding

Our work was supported by the National Natural Science Foundation of China (No.82074348, No. 82274491), the innovation and development joint project of Shandong Province Natural Science Foundation(ZR2023LZL009) and the Jinan clinical medical science and technology innovation plan (No. 202328072).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

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Contributor Information

Ye Yang, Email: 290422@njucm.edu.cn, Email: yangye876@sina.com.

Xing Cui, Email: cdz45@foxmail.com.

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Associated Data

Data Citations

Lee S, Ko MJ, Avritscher R, Lewandowski RJ, Kim D-H. ACS Nano Am Chem Soc. 2024;18:24269–82. 10.1021/acsnano.4c05809. Cryo-Nanocatalyst Enhances Therapeutic Efficacy of Cryo-Immunotherapy through Necroptosis and Local Delivery of Programmed Death-Ligand 1 Inhibitors.

Data Availability Statement

No datasets were generated or analysed during the current study.