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Facing challenges with hope: universal immune cells for hematologic malignancies.

Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation (allo-HSCT) has been widely implemented to treat hematologic malignancies. However, graft-versus-host disease (GVHD) and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life. In addition, GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions (DLIs) and chimeric antigen receptor (CAR) T-cell therapy. Because of the special immune tolerance characteristics and anti-tumor ability o

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 1 : National Harbor, MD, USA. 6-10 November 2019.

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Hijacking the helpers: platelet and neutrophil trafficking in AML and therapeutic exploitation.

Acute myeloid leukemia (AML) remains one of the most aggressive and treatment-resistant hematologic malignancies, driven by clonal expansion of immature myeloid blasts in the bone marrow and peripheral blood. Current therapies-chemotherapy and targeted agents-are limited by poor marrow penetration, systemic toxicity, and rapid development of resistant clones, leaving long-term survival rates low. Clinicians face the persistent challenge of delivering effective therapy while minimizing harm. Platelets and neutrophils-beyond their classical roles in hemostasis and innate immunity-actively suppor

Протеомический анализ показывает дисрегламентацию периферийных нейтрофилов крови у пациентов с множественным склерозом.

Множественный склероз (MS) представляет собой сложное автовоспалительное заболевание мозга и спинного мозга, которое приводит к аксоновому демилеляции и симптомам, включая усталость, боль и трудности с зрением и мобильностью. Вовлеченность иммунной системы в патологию MS хорошо известна, в частности адаптивная реакция T-клеток, и особое внимание уделяется производящему IL-17 поднабору клеток TH17 и их роли в вождении болезней. Однако важность врожденных иммунных клеток не была столь хорошо охарактеризована. Здесь мы сосредоточили внимание на нейтрофилах, которые являются врожденными иммунными

Staged Correction of Severe Thoracic Kyphosis in Patients with Multilevel Osteoporotic Vertebral Compression Fractures.

Study Design Technical report. Objective Multilevel osteoporotic vertebral compression fractures may lead to considerable thoracic deformity and sagittal imbalance, which may necessitate surgical intervention. Correction of advanced thoracic kyphosis in patients with severe osteoporosis remains challenging, with a high rate of failure. This study describes a surgical technique of staged vertebral augmentation with osteotomies for the treatment of advanced thoracic kyphosis in patients with osteoporotic multilevel vertebral compression fractures. Methods Five patients (average age 62 ± 6 years)

Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology.

Bispecific antibodies (bsAbs) have become an integral component of the therapeutic research strategy to treat cancer. In addition to clinically validated immune cell re-targeting, bsAbs are being designed for tumor targeting and as dual immune modulators. Explorative preclinical and emerging clinical data indicate potential for enhanced efficacy and reduced systemic toxicity. However, bsAbs are a complex modality with challenges to overcome in early clinical trials, including selection of relevant starting doses using a minimal anticipated biological effect level approach, and predicting effic

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

Долговременный иммунитет Т к вакцинам COVID-19 у пациентов MS при лечении истощения клеток B.

Защитная защита, обеспечиваемая вакцинами COVID-19 MRNA, связана с антиспайком (S) белка, нейтрализующим антитела. Тем не менее, юморальный иммунитет скомпрометирован в терапии B-клероза (BCD), используемой для лечения аутоиммунных заболеваний, таких, как множественный склероз (MS). Для изучения воздействия КБД на долговечность и эффективность защиты иммунитета, обусловленного вакцинацией, мы провели оценку реакции S-реактивных антител и Т-клеток за 1-70 недель после вакцинации в когортах MS, обработанных КБД, по сравнению с лечением, не связанным с БЦД, из четырех центров. Участники, прошедши

Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches.

Acute myeloid leukemia (AML) is clinically and genetically a heterogeneous disease characterized by clonal expansion of abnormal hematopoietic progenitors. Genomic approaches to precision medicine have been implemented to direct targeted therapy for subgroups of AML patients, for instance, IDH inhibitors for IDH1/2 mutated patients, and FLT3 inhibitors with FLT3 mutated patients. While next generation sequencing for genetic mutations has improved treatment outcomes, only a fraction of AML patients benefit due to the low prevalence of actionable targets. In recent years, the adoption of newer f

От Мауса к разуму: Нервозность роли орального микробиома в орофациальной боли и нейродегенерации.

Человеческая пероральная полость содержит разнообразный и динамичный микробиом, состоящий более чем из двух микробиомов. 700 Микробные виды, которые играют решающую роль в поддержании перорального и системного здоровья. Оральный дисбиоз, определяемый как нарушение этого микробного баланса, все чаще проявляется не только в периодонных заболеваниях, но и в патогенезе ородовой боли и нейродегенеративных заболеваниях. Были предложены ключевые патогены, такие, как Porphyromonas gingivalis, Treponema denticola и Fusobacterium нуклеатум, для высвобождения вирулентных факторов, включая липополисакчари

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects,

Does the Immunocompetent Status of Cancer Patients Have an Impact on Therapeutic DC Vaccination Strategies?

Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent status of cancer patients, which may facilitate tumor development by different mechanisms, including immune evasion. The most frequently used cellular vehicle in clinical trials are dendritic cells (DCs), thanks to their crucial role in initiating and directing immune responses. Viable va

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… Hyperthermia enhances CTL cross-priming. J. Immunol. 2006;176:2134–2141. doi: 10.4049/jimmunol.176.4.2134. 130. Prokopowicz Z.M., Arce F., Biedron R., Chiang C.L., Ciszek M., Katz D.R., Nowakowska M., Zapotoczny S., Marcinkiewicz J., Chain B.M. … Hypochlorous acid: A natural adjuvant that facilitates antigen processing, cross-priming, and the induction of adaptive immunity. J. Immunol. 2010;184:824–835. doi: 10.4049/jimmunol.0902606. 131. Mookerjee A., Graciotti M., Kandalaft L. …

Advances in nanotechnology-enabled adjuvants for peptide-based cancer vaccines.

Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials, which greatly reduces the risk of causing an undesired immune response and further improves the safety profile, garnering considerable interest in vaccine development. However, the immunogenicity induced by these peptides alone is not potent enough to elicit an effective immune response. Recently, combining the adjuvants with peptide antigens has shown promising effects to realize a satisfying immune response. In this review, we discuss the development of immunoadjuvants to enhance the safety and

Prescription and use of psychoactive medications among cancer patients and associated factors in lower and upper middle-income countries: systematic review.

PURPOSE: To describe the prescription and use of psychoactive medications among cancer patients in low- and middle-income countries (LMICs) and explore the factors influencing their prescription and use. METHODS: This systematic review was conducted following the PRISMA guidelines. Six electronic databases were searched. We included observational studies that investigated the prescription and use of psychoactive medications among adult cancer patients in low- and middle-income countries (LMICs) according to the 2024 World Bank's classification. Eligible studies specifically focused on the use

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unr

Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.

ABSTRACT: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Rec

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

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… SREC-1 | eHSP70, eHSP90 | Acts as a co-receptor with TLRs on APCs, essential for antigen uptake and cross-priming of T cells [ 81 ]. | In cancer cells, this same pathway promotes survival, proliferation, and metastasis. In lung cancer, eHSP70-RAGE signaling enhances tumor aggressiveness [ 118 ]. … Its primary described role is on APCs, where it acts as a co-receptor for TLRs and is essential for the uptake of eHSP–antigen complexes and the subsequent cross-priming of T cells. Its direct role in cancer cell biology is less established [ 81 ]. RAGE is another pattern-recognition receptor. …