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Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.

Cancer immunotherapy is a groundbreaking therapeutic strategy, yet it continues to face significant challenges, including limited overall response rates and treatment resistance. Emerging research has demonstrated the pivotal role of epigenetic modifications in tumor immune evasion, providing a strong rationale for developing "epi-immunotherapy"-an innovative approach that combines epigenetic therapy with immunotherapy. This comprehensive review systematically examines how epigenetic regulation mediates tumor immune escape and the mechanisms involved, including suppression of tumor antigen exp

From Selection to Use: Aptamers as Targeting Reagents in Hematology.

Aptamers are synthetic nucleic acid ligands that have been proposed as alternatives to antibodies for targeting molecules and cells. In hematology, most reviews have organized aptamer literature around diseases or technological platforms. This framing has obscured how unevenly different blood cell types have been covered. In this review, we present developed aptamers organized by blood cell lineages. Specifically, we examine aptamers for B cells, T cells, natural killer cells, and red blood cells. This organization revealed a strong concentration on a small set of canonical surface markers and

The therapeutic role of γδT cells in TNBC.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. As a result, conventional hormonal and targeted therapies are largely ineffective, underscoring the urgent need for novel treatment strategies. γδT cells, known for their robust anti-tumor properties, show considerable potential in TNBC treatment as they can identify and eliminate tumor cells without reliance on MHC restrictions. These cells de

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… Unlike αβT cells, some γδT cells do not undergo positive selection, making them unrestricted by Major histocompatibility complex (MHC) in their antigen recognition and killing capabilities ( 21 , 22 ). …

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

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… The αβ TCR complex, present in CD8 and CD4 T cells, allows recognition of peptides presented on the cell surface in the context of major histocompatibility complex (MHC) class I or class II, respectively. … They recognize specific antigens presented on major histocompatibility complex class I (MHC-I) molecules expressed on the surface of cancer cells. …

Recent advances and clinical pharmacology aspects of Chimeric Antigen Receptor (CAR) T-cellular therapy development.

Advances in immuno-oncology have provided a variety of novel therapeutics that harness the innate immune system to identify and destroy neoplastic cells. It is noteworthy that acceptable safety profiles accompany the development of these targeted therapies, which result in efficacious cancer treatment with higher survival rates and lower toxicities. Adoptive cellular therapy (ACT) has shown promising results in inducing sustainable remissions in patients suffering from refractory diseases. Two main types of ACT include engineered Chimeric Antigen Receptor (CAR) T cells and T cell receptor (TCR

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… Upon binding, an immunological synapse is formed between the CAR‐T cell and target cell, which occurs independently of the major histocompatibility complex (MHC) and antigen presentation, and results in the release of perforins and granzymes that trigger caspase dependent and independent apoptotic cell …

Advances and Hurdles in CAR T Cell Immune Therapy for Solid Tumors.

Chimeric antigen receptor (CAR) T cells in solid tumors have so far yielded limited results, in terms of therapeutic effects, as compared to the dramatic results observed for hematological malignancies. Many factors involve both the tumor cells and the microenvironment. The lack of specific target antigens and severe, potentially fatal, toxicities caused by on-target off-tumor toxicities constitute major hurdles. Furthermore, the tumor microenvironment is usually characterized by chronic inflammation, the presence of immunosuppressive molecules, and immune cells that can reduce CAR T cell effi

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… The risk of graft versus host reaction (GvHR) is minimal since the thymic selection of human T cells occurs in the context of mouse major histocompatibility complex (MHC) molecules [ 77 , 78 ]. …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

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… CTLA-4: cytotoxic T-lymphocyte-associated protein 4; TCR: T-cell receptor; PD-1: programmed cell death protein 1; PDL-1: programmed cell death ligand 1; MHC-I: major histocompatibility complex class I; GD2: disialoganglioside; CAR-T: chimeric antigen receptor T-cell; PC-CARs: peptide-centric chimeric …

The role of MSCs and CAR-MSCs in cellular immunotherapy.

Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem c

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… CARs can independently recognize tumor-associated antigens (TAAs) in the major histocompatibility complex (MHC) [ 2 – 6 ]. An unprecedented response rate was achieved following the use of CAR-T cells in the treatment of refractory B-cell malignancies [ 2 – 5 ]. …

Exosomes and organ-specific metastasis.

The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor metastasis and is critically modulated by exosomes and other mediators. Tumor-derived exosomes can promote epithelial-mesenchymal transition, angiogenesis, immune escape, formation of the pre-metastatic microenvironment, and transmission of drug-resistant molecules, thereby promoting tumor growth, invasion, and metastasis. Integrins are important regulatory molecules on exosomes that can locate metastatic cells at the initial stage of metastasis and show good

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… Ligands in exosomes, such as major histocompatibility complex (MHC) class I chain-related protein (MIC)A and MICB, downregulate NKG2D receptors by binding to them and inhibiting lymphocyte function, eventually leading to immune escape of tumor cells. 77 In terms of angiogenesis, miR-210 released by lung …

Cell Therapy: Types, Regulation, and Clinical Benefits.

Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review

ЦАРТ клетки в качестве новой терапевтической стратегии для множественных склерозов и других нейроиммунных расстройств.

В качестве трансформационного подхода к лечению множественных склерозов (MS) и других нейроиммунных расстройств, таких, как расстройства спектра нейромиелита (NMOSD), миелин олигодендроцита гликпротеина, связанных с антителами (MOGAD), и миастения гравис (MG), наряду с рядом других редких нейроиммунологических заболеваний, которые в настоящее время оцениваются в исследованиях, посвященных сочувствию или ранней фазе. Отчасти эти условия обусловлены автоматически реактивными клетками B, вызывающими хроническое воспаление и прогрессивное повреждение тканей. Несмотря на то, что нынешняя иммунодуля

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… While endogenous T-cells rely on antigen presentation through the Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) molecules, CAR T-cells are engineered to bypass this restriction by directly recognizing surface antigens on target cells [ 29 – 32 ]feature allows them to effectively …

Effects of pegylated G-CSF on immune cell number and function in patients with gynecological malignancies.

BackgroundPegylated granulocyte colony-stimulating factor (G-CSF; pegfilgrastim) is a longer-acting form of G-CSF, whose effects on dendritic cell (DC) and regulatory T cell (Treg) mobilization, and on the in vivo and ex vivo release of immune modulating cytokines remain unexplored.MethodsTwelve patients with gynecological cancers received carboplatin/paclitaxel chemotherapy and single-dose pegfilgrastim as prophylaxis of febrile neutropenia. Peripheral blood was collected prior to pegfilgrastim administration (day 0) and on days +7, +11 and +21, to quantify immunoregulatory cytokines and to a

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… Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995;182:389–400. doi: 10.1084/jem.182.2.389. …

Senescent T cells: Beneficial and detrimental roles.

As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells toward replicative senescence, due to telomere erosion. This review discusses mechanisms that regulate the end-stage differentiation (senescence) of T cells. Although these cells, within both CD4 and CD8 compartments, lose proliferative activity after antigen-specific challenge, they acquire innate-like immune function. While this may confer broad i

Natural Killer Cells: Angels and Devils for Immunotherapy.

In recent years, the relevance of the immune system to fight cancer has led to the development of immunotherapy, including the adoptive cell transfer of immune cells, such as natural killer (NK) cells and chimeric antigen receptors (CAR)-modified T cells. The discovery of donor NK cells' anti-tumor activity in acute myeloid leukemia patients receiving allogeneic stem cell transplantation (allo-SCT) was the trigger to conduct many clinical trials infusing NK cells. Surprisingly, many of these studies did not obtain optimal results, suggesting that many different NK cell parameters combined with

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… Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature. 2005;436:709–713. doi: 10.1038/nature03847. 50. Shah N., Martin-Antonio B., Yang H., Ku S., Lee D.A., Cooper L.J.N., Decker W.K., Li S., Robinson S.N., Sekine T., et al. …

Evolving Paradigms in Chronic Graft-Versus-Host Disease: From Global Immunosuppression to Precision Targeted and Cell-Based Therapies.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment for a range of medical conditions. However, the procedure carries with it a significant risk of chronic graft-versus-host disease (cGVHD), which can have a considerable impact on patients’ quality of life and clinical outcomes. In recent years, there has been a marked shift in treatment strategies for this condition, with greater emphasis being placed on novel targeted therapies and cell therapies that target specific pathways. This shift in approach signifies a more profound comprehension of the pa

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… Initially, donor T cells recognize host major histocompatibility complex (MHC) antigens or minor histocompatibility antigens (mHA) presented by host antigen-presenting cells (APCs), which results in T cell activation(e.g., Th17, Tfh) while concurrently suppressing Treg cell numbers and function [ 29 …

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

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… CAR‐T cell therapy by engineering T cells to express synthetic receptors that recognize tumor‐associated antigens in a major histocompatibility complex (MHC)‐independent way has shown huge success in hematological malignancies. … Such chronic activation of ER stress modulates the TME by reducing the surface expression of major histocompatibility complex class 1 and 2 proteins, thereby impeding immune recognition of the cancer cells by NK cells [ 183 , 184 ]. …

Revolutionizing in vivo therapy with CRISPR/Cas genome editing: breakthroughs, opportunities and challenges.

Genome editing using the CRISPR/Cas system has revolutionized the field of genetic engineering, offering unprecedented opportunities for therapeutic applications in vivo. Despite the numerous ongoing clinical trials focusing on ex vivo genome editing, recent studies emphasize the therapeutic promise of in vivo gene editing using CRISPR/Cas technology. However, it is worth noting that the complete attainment of the inherent capabilities of in vivo therapy in humans is yet to be accomplished. Before the full realization of in vivo therapeutic potential, it is crucial to achieve enhanced specific

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… To address these concerns, researchers have explored different Cas9 orthologs and AAV serotypes based on sequence similarities and predicted binding strength to major histocompatibility complex (MHC) class I and class II molecules. …

Immune-based combination therapy for esophageal cancer.

Esophageal cancer (EC) is an aggressive malignancy raising a healthcare concern worldwide. Standard treatment options include surgical resection, chemotherapy, radiation therapy, and targeted molecular therapy. The five-year survival rate for all stages of EC is approximately 20%, ranging from 5% to 47%, with a high recurrence rate and poor prognosis after treatment. Immunotherapy has shown better efficacy and tolerance than conventional therapies for several malignancies. Immunotherapy of EC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, has shown clinica

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… The CAR molecule is major histocompatibility complex (MHC)-independent, and recognition and binding of specific antigens primarily depend on extracellular domains, namely single chain variable fragments ( 68 ). …

T-Cell Acute Lymphoblastic Leukemia-Current Concepts in Molecular Biology and Management.

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are

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… Only those DN cells that have successfully rearranged TCRβ chain transform to double positive (DP) cells expressing CD4 and CD8, at which point they cease to proliferate and undergo rearrangement of the TCRα chain to form a complete TCR that can recognize MHC (major histocompatibility complex). …

Immune defects in the risk of infection and response to vaccination in monoclonal gammopathy of undetermined significance and multiple myeloma.

The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal immunoglobulin. They typically affect an older population, with median age of diagnosis of approximately 70 years. In both disorders, there is an increased risk of infection due to the immunosuppressive effects of disease and conjointly of therapy in MM, and response to vaccination to counter infection is compromised. The underlying factors in

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… To examine T-cell response to infectious agent antigens, Maecker et al. characterized the in vitro CD8+ T-cell response in HLA-A*0201+ MM patients and healthy individuals to influenza A and Epstein–Barr virus-derived immunodominant epitopes using major histocompatibility complex (MHC)/peptide tetramers …