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Paraneoplastic Neurological Syndromes: Advances and Future Perspectives in Immunopathogenesis and Management.

Paraneoplastic neurological syndromes (PNSs) are immune-mediated disorders caused by an antitumor response that cross-reacts with the nervous system, leading to severe and often irreversible neurological disability. Once considered exceedingly rare, PNSs are now increasingly recognized owing to the identification of novel neural autoantibodies, wider use of commercial testing, and the emergence of immune checkpoint inhibitor (ICI)-related neurotoxicity that phenotypically overlaps with classic PNS. In this narrative review, we performed a structured search of PubMed/MEDLINE, Scopus, Web of Sci

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… The primary pathogenic effectors are CD8+ cytotoxic T-cells that recognize neuronal peptides presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of neurons [ 31 ]. …

Targeting tumor immunosuppressive microenvironment for pancreatic cancer immunotherapy: Current research and future perspective.

Pancreatic cancer is one of the most malignant tumors with increased incidence rate. The effect of surgery combined with chemoradiotherapy on survival of patients is unsatisfactory. New treatment strategy such as immunotherapy need to be investigated. The accumulation of desmoplastic stroma, infiltration of immunosuppressive cells including myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs), as well as tumor associated cytokine such as TGF-β, IL-10, IL-35, CCL5 and CXCL12 construct an immunosuppres

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… TGF-β secreted by CAFs induces DCs to down regulate the major histocompatibility complex (MHC) class II molecules and costimulatory molecules such as CD40, CD80 and CD86, thus decreasing their ability to activate cytotoxic T cell responses and their antigen presenting function ( 35 ). …

Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance.

Chimeric Antigen Receptor (CAR) T cell therapies - adoptive T cell therapies that have been genetically engineered for a new antigen-specificity - have displayed significant success in treating patients with hematologic malignancies, leading to three recent US Food and Drug Administration approvals. Based on the promise generated from these successes, the field is rapidly evolving to include new disease indications and CAR designs, while simultaneously reviewing and optimizing toxicity and management protocols. As such, this review provides expert perspective on the significance and clinical c

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… As such, researchers have developed strategies to increase tumor recognition of adoptively stimulated cells outside of T cell receptor (TCR)/major histocompatibility complex (MHC)/peptide recognition. … Food and Drug Administration Fludarabine/cyclophosphamide Granulocyte macrophage colony stimulating factor Good manufacturing practice Graft vs host disease Hematopoietic stem cell transplant Interferon Interleukin Major histocompatibility complex Minimal residual disease Neurotoxicity Objective …

Research progress on tumor-infiltrating lymphocyte therapy for cervical cancer.

Cervical cancer is a common malignant tumor in women, and human papillomavirus (HPV) infection is a major cause of cervical cancer. Tumor-infiltrating lymphocytes (TILs) are a heterogeneous group of lymphocytes primarily composed of T lymphocytes found within the tumor parenchyma and stroma. These cells can be isolated from tumor tissue, activated, expanded in vitro, and reinfused into the patient to exert an anti-tumor immune effect. As a form of personalized immunotherapy, TILs therapy has shown satisfactory efficacy and safety in advanced recurrent and metastatic cervical cancer, offering n

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… HPV, Human papilloma virus;MHC-I, Major Histocompatibility Complex Class I molecules;MHC-I, Major Histocompatibility Complex Class I molecules;CXCL10, Human Chemokine (C-X-C motif) ligand 10;TLR, Toll-like receptors;IL-2R, Interleukin 2 receptor;IFN, Interferon;TGF-β, Transforming growth factor-β. … After the TILs enter the patient’s body, CD4+ T cells bind to major histocompatibility complex (MHC) II, assisting and regulating the immune response. …

γδ T cells in hematological malignancies: mechanisms and therapeutic strategies.

γδ T cells are a unique subset of lymphocytes with both innate and adaptive features. They recognize and eradicate various hematological malignancies through different mechanisms, employing factors including γδ TCR, NKR, NKG2D, TRAIL, and perforin/granzyme. They also modulate other immune cells to enhance their antitumor activity. Moreover, γδ T cells have potent antiviral functions after hematopoietic stem cell transplantation (HSCT), which may improve the outcome of patients with hematological malignancies. In this review, we summarize the current knowledge on γδ T cell biology and function

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… Unlike conventional αβ T cells that recognize peptide antigens presented by major histocompatibility complex (MHC) molecules, γδ T cells recognize nonpeptide antigens such as phosphoantigens (PAgs) or stress-induced molecules in an MHC-unrestricted manner. 3 , 4 Therefore, γδ T cells can respond rapidly … Lethal murine graft-versus-host disease induced by donor gamma/delta expressing T cells with specificity for host nonclassical major histocompatibility complex class Ib antigens. Blood 1996;87(2):827–837. [77] Pabst C, Schirutschke H, Ehninger G, Bornhäuser M, Platzbecker U. …

Canine cancer immunotherapy studies: linking mouse and human.

Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and co

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… Interestingly, there is evidence for breed effects on immune function which likely relate to the inheritance of particular haplotypes of major histocompatibility complex (MHC) genes and further reinforce the paradox that dogs are a highly outbred species which nevertheless manifest significant effects … Abbreviations Chimeric antigen receptor T cell Computed tomography Canine thyroid adenocarcinoma Cytotoxic T-lymphocyte-associated antigen 4 Genetically engineered mice Indolamine-2,3 dioxygenase monoclonal antibody Major histocompatibility complex Non-human primates Natural killer Non-small …

A Deep Dive Into the Newest Avenues of Immunotherapy for Pediatric Osteosarcoma: A Systematic Review.

Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment with combinations of surgery and chemotherapy for the localized OS has only brought minuscule improvements in prognosis. In comparison, the advanced, metastatic, or recurrent forms of OS are often non-responsive to chemotherapy, adding to the dire need to develop new and efficient therapies. The question of interest investigated in this systematic review is whether immunotherapy can play a meaningful role in improving the clin

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… Abbreviations – CTLA-4: cytotoxic T-lymphocyte associated protein 4; PD-L1: programmed death-ligand 1; PD-1: programmed cell death protein 1; TCR: T-cell receptor; MHC: major histocompatibility complex; NY-ESO-1: New York esophageal squamous cell carcinoma 1; HLA: human leukocyte complex; IGF-1R: insulin-like …

Биоразлагаемые и стимульно-реагирующие наноматериалы для адресной доставки лекарств в аутоиммунных заболеваниях.

Аутоиммунные заболевания создают сложные терапевтические проблемы из-за их хронического характера, системного воздействия и требования к точному иммунодуляции во избежание негативных побочных эффектов. Недавние достижения в области биоразлагаемых и стимулирующих наноматериалов открыли новые возможности для адресных систем доставки наркотиков, способных решать эти проблемы. Этот обзор содержит всеобъемлющий анализ современных биоразлагаемых нанокарьеров, таких, как полимерные наночастицы, липосомы и гидрогели, разработанные для целевой доставки в аутоиммунную терапию. Эти наноматериалы предназн

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… When antigen-presenting cells present pathogen-derived peptides on major histocompatibility complex (MHC) molecules, T cell receptors (TCRs) recognize these peptides and initiate an immune response. … Legend: MHC (Major Histocompatibility Complex); TCR (T Cell Receptor). 1.2. Overview of Nanotechnology in Drug Delivery Nanotechnology is an interdisciplinary field that involves the design, fabrication, and application of materials at the nanoscale (typically ranging from 1 to 100 nm). …

Role of the osteocyte in bone metastasis - The importance of networking.

Metastatic bone disease is a complex condition resulting from the migration and colonization of cancer cells from their primary site to the bone microenvironment, where they typically develop a metastatic niche. Osteocytes, the most abundant cells in bone tissue and the master regulators of bone remodelling, are increasingly thought to play a crucial role in this process through intricate interactions with cancer cells. This review covers the recent progress made in exploring the multifaceted interactions between osteocytes and cancer cells in the metastatic microenvironment, highlighting the

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… A novel signalling pathway recently identified in the multiple myeloma lesion microenvironment is the major histocompatibility complex class II transactivator (CIITA) in osteocytes, which myeloma cells can activate by producing 2-deoxy-D-ribose (2DDR) [36] . …

Oncolytic viruses on the cusp of success?: proceedings of the 9th International Conference on Oncolytic Virus Therapeutics

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… To block rodent TAP and major histocompatibility complex class 1 antigen presentation, Matthew Mulvey (BeneVir Biopharm, Rockville MD) inserted the bovine herpesvirus UL49.5 gene, which inhibits both mouse and human TAP, into oHSV. …

Progress of immune senescence in multiple myeloma treatment resistance.

Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment

Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.

Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs). Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish th

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… Genetically engineered T cells, which are illustrated in Figure 1 , express chimeric antigen receptors (CARs) targeted to cancer cells and can identify tumor-associated antigens (TAAs) located on the surface of cancerous cells irrespective of their expression of the major histocompatibility complex [ … Abbreviations CAR-T cells—chimeric antigen receptor T cell; TAAs—tumor-associated antigens; TAMs—tumor-associated macrophages; MHC-I—major histocompatibility complex I; DNA—deoxyribonucleic acid; RNA—ribonucleic acid; TCD8+—cluster of differentiation 8+ T cells; T-VEC—talimogene laherparepvec; VSV—vesicular …

Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy.

Plasmacytoid dendritic cells (pDCs) are multifaceted immune cells with a wide range of innate and adaptive immunological functions. They constitute the first line of defence against multiple viral infections and have also been reported to actively participate in antitumor immune responses. The clinical implication of the presence of pDCs in the tumor microenvironment (TME) is still ambiguous, but it is clear that pDCs possess the ability to modulate tumor-specific T cell responses and direct cytotoxic functions. Therapeutic strategies designed to exploit these qualities of pDCs to boost tumor-

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… The major group of specialized APCs involved in effector T-cell priming includes Dendritic cells (DCs), which process and present TAAs on major histocompatibility complex (MHC) molecules acquired from the tumor microenvironment (TME) [ 2 ]. … histocompatibility complex moDCs | Monocyte-derived dendritic cells NK | Natural killer OS | Overall survival PBMCs | Peripheral blood mononuclear cells pDCs | Plasmacytoid DCs PFS | Progression-free survival PGE2 | Prostaglandin E2 SLN | Sentinel lymph node TAA | Tumor-associated antigens TGF-β | Transforming …

NK92 Разоблачение антиBCMA CAR и Secreted TRAIL для лечения множественной миеломы: предварительная оценка in Vitro.

Множественная миелома (ММ) стала свидетелем улучшения качества жизни пациентов благодаря совершенствованию терапевтических подходов. В частности, аллогенная трансплантация стволовых клеток, протеаозные ингибиторы, иммуномодулятивные препараты и моноклонные антитела способствовали повышению качества жизни. Недавно появилась многообещающая авеню с клетками химерика антигенного рецептора (CAR) Т, направленными против антигена созревания клеток B-клеток (BCMA), широко выраженная на клетках MM. Чтобы уменьшить риски, связанные с аллогенными Т-клетками, мы изучили потенциал выражения BCMA CAR в нату

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… To do so, they can identify a foreign or missing class-I major histocompatibility complex (MHC-I) on their target [ 22 ], leading to their activation and release of perforins that create pores in the target’s membrane and granzymes which induce apoptosis by cleaving pro-apoptotic molecules [ 23 ]. … histocompatibility complex (S)MM | (smoldering) multiple myeloma mRNA | (messenger) ribonucleic acid NK | natural killer Nluc | nanoluc luciferase P/S | penicillin/streptomycin PI | proteasome inhibitor TCR | T cell receptor TNF-α | tumor necrosis factor alpha wt | wild-type Appendix A Figure A1 Overview …

Полиморфизм HLA в нейроиммунных болезнях: увязка представления антигенов с нейроинфламматическими программами.

Полиморфизм человека антигена лейкоцита (HLA) формирует антигенное представление и подверженность иммунизированным заболеваниям. В нейроиммунных расстройствах главный вопрос заключается в том, как зависимость от HLA антигенная видимость превращается в специфический иммунитет от болезней и повреждение тканей. В этом Обзоре мы интегрируем генетические, молекулярные, клеточные и клинические данные по множеству склерозов (MS), расстройству спектра нейромиелитов, синдрому Гильен-Барре, нарколепсии, аутоиммунальному энцефалиту и миастении гравис. :: HLA-DR15-MS Ось является наиболее механистически р

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… Linkage disequilibrium, extended haplotypes, and ancestry The major histocompatibility complex is gene dense and contains extensive linkage disequilibrium (LD). …

Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.

Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti-tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co-inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti-tumor immune response and promote immune-mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been first

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… Abbreviation: APC, antigen‐presenting cells; CTLA‐4, cytotoxic T‐lymphocyte‐associated protein 4; FGL‐1, fibrinogen‐like protein 1; Gal‐9, galectin‐9; HVEM, herpes virus entry mediator; LAG‐3, lymphocyte activation gene 3; MHC, major histocompatibility complex; NK cells, natural killer cells; PD‐1, programmed … Additional inhibitory immune checkpoints related to NK cells, apart from the inhibitory receptors linked to the major histocompatibility complex (MHC) class I, have been discovered, including the well‐known checkpoints like CTLA‐4, PD‐1, LAG‐3, and T cell immunoglobulin domain and mucin domain 3 (TIM …

Biomarkers in individualized management of chimeric antigen receptor T cell therapy.

The development of chimeric antigen receptor (CAR) T cell immunotherapy has achieved promising results, both in clinical studies and in commercial products for patients with hematologic malignancies. Despite high remission rates of CAR-T cell therapy in previously untreatable, refractory and/or relapsed patients, several challenges in CAR-T therapy remain to be overcome, especially in integrating such therapies into personalized disease management approaches. Given the unique characteristics of CAR-T therapy, it is particularly urgent to identify biomarkers to maximize their clinical benefits.

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… Background With no restriction to major histocompatibility complex (MHC) [ 1 ], chimeric antigen receptor (CAR) -T cells have been a breakthrough in personalized cancer therapy, especially in hematological malignancies. … histocompatibility complex Complete remission Multiple myeloma CAR-related encephalopathy syndrome Minimal residual disease C-reactive protein Memorial Sloan Kettering Cancer Center Cytokine release syndrome National Cancer Institute Cerebrospinal fluid Non- Hodgkin's lymphoma Common Terminology …

Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions.

Adoptive cell therapy (ACT) has emerged as a transformative strategy in cancer immunotherapy, offering durable clinical benefit in hematologic malignancies and expanding therapeutic potential in solid tumors. However, the translation of ACT to solid malignancies remains constrained by biological, immunological, and logistical challenges. This narrative review provides an evidence based overview of the current clinical landscape of ACT in solid tumors, with a focus on chimeric antigen receptor T cell (CAR-T), tumor-infiltrating lymphocyte (TIL), and T cell receptor-engineered T cell (TCR-T) the

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… histocompatibility complex (MHC) presentation ( 7 , 8 ). … Unlike CAR-T cells, TCR-T cells recognize intracellular tumor proteins as short peptides presented on major histocompatibility complex (MHC)/human leukocyte antigen (HLA) molecules, making this approach inherently HLA-restricted ( 64 ). …

Development of fever following first administration of zoledronate as a prognostic factor in advanced non-small cell lung cancer patients with bone metastases.

Nitrogen-containing bisphosphonates (N-BPs), which are usually used for the treatment of advanced cancer with bone metastasis, occasionally cause fever following the first administration. However, it is unclear as to how the development of fever following the first administration of N-BP is associated with clinical outcome. The aim of the present study was to determine the prognostic value of the development of fever following the first administration of N-BP in advanced non-small cell lung cancer patients with bone metastases. The present study reviewed the data of 46 patients with advanced n

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… ZOL-related fever is associated with the activation of γδ T cells, which recognize non-peptide antigens in a major histocompatibility complex-unrestricted manner ( 15 ). γδ T cells have demonstrated cytotoxicity against a variety of cell lines in vitro , including peripheral blood mononuclear cells from …

Chimeric antigen receptor T-cell therapy: challenges and opportunities in lung cancer.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the paradigm in hematological malignancies treatment, driving an ever-expanding number of basic research and clinical trials of genetically engineering T cells to treat solid tumors. CAR T-cell therapies based on the antibodies targeting Mesothelin, CEA, EGFR, EGFR, MUC1, DLL3, and emerging novel targets provide promising efficacy for lung cancer patients. However, clinical application of CAR T-cell therapy against lung cancer remains limited on account of physical and immune barriers, antigen escape and heterogeneity, on-target

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… The antigen-binding domains of CARs are generally single-chain variable fragments (scFv) targeting tumor-associated antigens (TAA), thus conferring major histocompatibility complex (MHC)-independent T cell activation [ 4 ]. … Lack and restoration of sensitivity of lung cancer cells to cellular attack with special reference to expression of human leukocyte antigen class I and/or major histocompatibility complex class I chain related molecules A/B. Cancer Sci 2007; 98: 1795–802. 6. …