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Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly aggressive malignant tumor. Traditional therapeutic approaches have limited efficacy in locally advanced HNSCC patients, and neoadjuvant immunotherapy has emerged as a new hope. However, the current outcomes of neoadjuvant immunotherapy for HNSCC are not yet optimal and urgently need improvement. This article comprehensively reviews the clinical research progress of neoadjuvant immunotherapy in the field of HNSCC treatment. By integrating perspectives from the regulatory mechanisms of the immune microenvironment, we propose future resea

OCA-B promotes pathogenic maturation of stem-like CD4+ T cells and autoimmune demyelination.

Stem-like T cells selectively contribute to autoimmunity, but the activities that promote their pathogenicity are incompletely understood. Here, we identify the transcription coregulator OCA-B as a driver of the pathogenic maturation of stem-like CD4+ T cells to promote autoimmune demyelination. Using 2 human multiple sclerosis (MS) datasets, we show that POU2AF1, the gene encoding OCA-B, is elevated in CD4+ T cells from patients with MS. We show that T cell-intrinsic OCA-B loss protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to viral CNS infection

Вирус Эпштейн-Барр, витамин D и иммунная реакция: связи с последствиями множественного склероза.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS) без какого-либо окончательного запуска. Однако эпидемиологические исследования показывают, что важными факторами риска являются такие экологические факторы, как инфекция вируса Эпштейн-Барр (ЭБВ) и низкий уровень витамина D (вид D) у генетически предрасположенных лиц. Одно из ведущих предложений заключается в том, что EBV приводит в действие MS с помощью таких механизмов, как молекулярная имитация, где активированные автоматически реактивные B и T лимфоциты ошибочно нацелены на самоантигены. В соответствии

CAR-T State of the Art and Future Challenges, A Regulatory Perspective.

This review is an outlook on CAR-T development up to the beginning of 2023, with a special focus on the European landscape and its regulatory field, highlighting the main features and limitations affecting this innovative therapy in cancer treatment. We analysed the current state of the art in the EU and set out a showcase of the field's potential advancements in the coming years. For this analysis, the data used came from the available scientific literature as well as from the European Medicines Agency and from clinical trial databases. The latter were investigated to query the studies on CAR

Регулирование питания иммунной системы кишечного мозга происходит на протяжении всей жизни.

Иммунная ось кишечника объединяет микробные, иммунные и нейронные сигналы для регулирования нейроразвития, гомеостаза и подверженности болезням. Раннее питание, в частности молочные олигозакариды, формирует благотворный микробиотический состав, повышает гиппокампальную пластичность, способствует антивоспалительной микроглианской поляризации и поощряет иммунную терпимость. Микробиота - метаболиты гута, включая короткоцепные жирные кислоты, производные триптофана и вторичные желчные кислоты, регулируют микроглиатическое созревание, функцию астроцита, дифференциацию клеток Т, производство нейротр

What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Various Inflammatory Diseases Associated With Bone Loss?

Local priming of osteoclast precursors (OCp) has long been considered the main and obvious pathway that takes place in the human body, where local bone lining cells and RANKL-expressing osteocytes may facilitate the differentiation of OCp. However, priming of OCp away from bone, such as in inflammatory tissues, as revealed in peripheral blood, may represent a second pathway, particularly relevant in individuals who suffer from systemic bone loss such as prevalent in inflammatory diseases. In this review, we used a systematic approach to review the literature on osteoclast formation in peripher

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

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

Exercise-mobilized donor lymphocyte infusions enhanced with cytokine stimulation for the prevention and treatment of leukemic relapse after allogeneic hematopoietic cell transplantation.

Donor lymphocyte infusions (DLI) are a standard therapy following allogeneic hematopoietic cell transplantation (alloHCT) for preventing and treating leukemic relapse in high-risk patients, particularly those with myeloid malignancies such as acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). However, the efficacy of DLI remains suboptimal and is accompanied by a significant risk of life-threatening graft-versus-host disease (GvHD), highlighting the urgent need for strategies that enhance graft-versus-leukemia (GvL) effects while mitigating GvHD.

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms.

Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPN) are neoplastic diseases of the hematopoietic stem cells in the bone marrow. MPN are characterized by chronic inflammation and immune dysregulation. Of interest, the potent immunostimulatory cytokine interferon-α has been used to treat MPN for decades. A deeper understanding of the anti-cancer immune response and of the different immune regulatory mechanisms in patients with MPN has paved the way for an increased perception of the potential of cancer immunotherapy in MPN. Therapeutic vaccination targeting the driver mut

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… IFN-α enhances antigen presentation, cross-priming, the maturation of dendritic cells, and the cytotoxic capabilities of cytotoxic T-lymphocytes and NK cells and suppresses the inhibitory capacity of MDSC and Treg. … Type I interferons as stimulators of DC-mediated cross-priming: Impact on anti-tumor response Front. Immunol. 2013 4 483 10.3389/fimmu.2013.00483 24400008 PMC3872318 99. Bracci L. Proietti E. Belardelli F. IFN-alpha and novel strategies of combination therapy for cancer Ann. N. Y. Acad. …

Real-World Data Included in Post-authorisation Measures: A Case Study of Approved Advanced Therapy Medicinal Products in the European Union between 2013 and 2024.

BackgroundAdvanced therapy medicinal products (ATMPs) often require long-term monitoring to assess both safety and efficacy post-authorisation due to uncertainties identified during the approval process. This study aims to characterise the use of real-world data (RWD) in post-authorisation measures (PAMs) for ATMPs approved in the European Union.MethodsA systematic extraction of all PAMs from publicly available European Medicines Agency (EMA) regulatory documents for ATMPs approved between January 2013 and December 2024 was performed, followed by the identification of the presence and sources

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

BackgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (MethodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.ResultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive

Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies.

A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (

Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma.

Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammatio

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… First, radiation facilitates the cross-priming of CTLs, and secondly, radiation has an abscopal effect. Radiation enhances cross-priming of CTLs in two ways. … This signal facilitates the cross-priming of CTLs. In addition, radiation induces the release of danger-associated molecular patterns (DAMPs) including ATP and HMGB-1. These DAMPs are endogenous immune adjuvants that stimulate DC activation, facilitating cross-priming of CTLs[ 51 ]. …

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, December 5th 2015

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… Hurdles in vaccination with polypeptides include, first of all, relatively weak T cell responses (narrow focused and short lived), then inadequate induction of CD8 T cells by LSPs and recombinant proteins (cross priming), and, finally, local immunosuppression. … New studies, including cross-priming of CD137 with DC and combination of immunostimulatory monoclonal antibodies anti-hCD137 (urelumab) with anti-hPD-1 (nivolumab) are presenting promising results. …

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

Клемастин фумарат ускоряет аккумуляцию инвалидности в прогрессивном множественном склерозе, усиливая пироптоз.

Множественный склероз (MS) — иммунопосредованное демиелинизирующее заболевание центральной нервной системы (CNS). Клемастин фумарат, внезапный антигистамин и мускариновый блокатор рецепторов, обладает ремиелионирующим потенциалом в MS. Климастичная рука была добавлена в текущее клиническое испытание платформы TRAP-MS ( " TRP-MS " )NCT03109288) для выявления сигнатуры ремиелинирования цереброспиновой жидкости (CSF) и для сбора данных о безопасности клемастина у пациентов независимо от рецидива (PIRA). Клемастинская рука была остановлена в соответствии с определенными протоколом критер

Безопасность и эффективность антиклеточных антигенных (Анти-БКМА) антител для релапсированных/отверженных миеломы: систематический обзор клинических испытаний.

Многократная миелома (RRMM) по-прежнему является сложным заболеванием и нуждается в более эффективных вариантах лечения. В настоящее время проводятся клинические испытания, в ходе которых проводится анализ воздействия антиклеточного антигена (BCMA) биконкретного антитела (Abs) против RRMM с ранними многообещающими результатами. Целью этого исследования является систематическая оценка безопасности и эффективности антибиологических антител для пациентов с RRMM. На сайте PubMed, Embase, Web of Science и Американского общества гематологии (ASH) были найдены опубликованные данные о безопасности и э

Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma.

Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells (APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppre

The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte