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Mycobiota и Antifungal Antibodies как новые целевые показатели для диагностики и прогнозирования болезней человека.

Человеческое тело колонизируется различными микроорганизмами, при этом наиболее активно изучаются бактерии. Однако грибы, которые в совокупности известны как «микобиота», все чаще признаются в качестве составных компонентов микробиоты, населяющей почти все мукосальные поверхности. Комменсальные грибы оказывают влияние на иммунитет хост-приемника, как и бактерии, и способствуют выполнению других важных функций, включая метаболизм. В этом новом понимании грибы рассматриваются как потенциальные биомаркеры для диагностики и прогнозирования различных заболеваний. В этом обзоре мы изучаем двойную ро

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… Activation of Adaptive Immunity Fungi recognition triggers the processing of fungal proteins into small antigenic peptides, which are then combined with major histocompatibility complex (MHC) molecules. … histocompatibility complex MS Multiple sclerosis nAbs Natural antibodies NGS Next-generation sequencing PAMPs Pathogen-associated molecular patterns PBC Primary biliary cirrhosis PD Parkinson’s disease PMNs Polymorphonuclear leukocytes PRRs Pattern recognition receptors PSC Primary sclerosing cholangitis …

NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in hematologic malignancies, but its efficacy in solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment (TME) that hinders CAR-T cell trafficking and function. NKG2D CAR-T cells, which target stress-induced NKG2D ligands (NKG2DLs) broadly expressed on tumor cells, have shown promising potential in overcoming the immunosuppressive barriers of the solid TME. This review highlights recent advances in NKG2D CAR-T cell strategies for solid tumors, including innovations in CAR archite

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… Initial CAR designs focused on enabling major histocompatibility complex (MHC)-independent antigen recognition, evolving from simple antibody-based constructs to sophisticated multidomain receptors that incorporate co-stimulatory and cytokine signaling components ( 48 ). … Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity . …

CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment.

Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, prol

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… Caribou Biosciences, Inc. | 50 Metastatic Nonsmall cell lung cancer | NCT02793856 | Programmed cell death protein 1 (PD-1) | — | Ex-vivo | 1 | Sichuan University | 12 Renal cell carcinoma | NCT04438083 | Anti-CD70 CAR, Major histocompatibility complex class I (MHC-I), T-cell receptor (TCR) | — | Ex-vivo … histocompatibility complex I (MHC- I) knock-in of anti-CD19 CAR | Gene knock-out, gene insertion | Ex-vivo | 1 | CRISPR Therapeutics AG | 143 Role of CRISPR/Cas9 in Human Cancers Cancer is the second most common cause of death across the world, representing around 8.8 million passing in 2015. …

Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives.

Cancer immunotherapy is a type of treatment that harnesses the power of the immune systems of patients to target cancer cells with better precision compared to traditional chemotherapy. Several lines of treatment have been approved by the US Food and Drug Administration (FDA) and have led to remarkable success in the treatment of solid tumors, such as melanoma and small-cell lung cancer. These immunotherapies include checkpoint inhibitors, cytokines, and vaccines, while the chimeric antigen receptor (CAR) T-cell treatment has shown better responses in hematological malignancies. Despite these

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… Antigen-presenting dendritic cells then capture these antigens and process them to create peptides that bind to the major histocompatibility complex (MHC) and are then presented to T cells. The CD4+ T-cell receptors can identify the peptide-MHC-II molecules. … Next, the DCs move to the lymph nodes, where they present TAs via major histocompatibility complex class II (MHC-II), which binds with receptors on naive CD4 T cells. Co-stimulation occurs when the CD80/86 (B7) on the DCs binds with the CD28 ligand on CD4+ T cells. …

Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and su

Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular p

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… Yet, in the face of tissue injury, cell death or microbial infection, DCs are activated and migrate to the draining lymph nodes (LN) where they acquire fully mature phenotype (i.e, high expression of major histocompatibility complex (MHC) molecules and co-stimulatory signaling potential). … Additionally, immunogenic tumor clones (represented in pink) have their antigenicity increased by up regulating major histocompatibility complex class I (MHC-I) molecules. …

Immunotherapy Strategies Against Multiple Myeloma

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… Natural killer cells can mediate the lysis of cells that express decreased major histocompatibility complex class I (MHC I) levels, such as virally infected or tumor cells. … histocompatibility complex class I multiple myeloma natural killer T cells peripheral blood mononuclear cells programmed death 1 radioimmunotherapy stable disease tumor-associated antigens US Food and Drug Administration. …

IFNIKB: база данных типов I интерферонов для исследований антитуморной иммунности.

Тип I интерферон (ИФН-I) представляет собой важный класс цитокинов, способных ингибировать прогрессирование опухоли через механизмы, такие как иммуномодуляция опухолевого микросреды или воздействие на клеточные компоненты. Несмотря на то, что разработаны различные эндогенные и экзогенные терапевтические стратегии ИФН-I, отчеты о нарушении функции иммунных клеток, вызванных усилением сигнала ИФН-I, указывают на то, что оптимальные стратегии еще не установлены. Однако данные по ИФН-I в настоящее время распределены по нескольким публичным базам данных и отсутствуют систематическая интеграция, что

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… Differential induction by interferons of major histocompatibility complex-encoded and non-major histocompatibility complex-encoded antigens in human breast and ovarian carcinoma cell lines. Cancer Res. 1989;49:2928–34., 7. Yadav D, Ngolab J, Lim R S et al. …

Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy.

Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls of conventional anticancer therapies such as systematic toxicity, compromised life quality, and limited to severe side effects are major areas of concern of conventional cancer treatment approaches. Owing to the expansion of knowledge and technological advancements in the field of cancer biology, more innovative and safe anti-cancerous approaches such as immune therapy, gene therapy and targeted therapy a

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… These TAs stimulate cellular and/or humoral responses, giving rise to antigenic determinants presented as major histocompatibility complex (MHC) class I molecules at the surface of tumor cells to incite CD8+ T cells [ 11 ]. …

Автоматизированная радиомасса для прогнозирования реакции терапии и минимальных остаточных заболеваний от базовой МРТ в множестве миеломы.

Это многоцентровое исследование снимков было направлено на создание и проверку автоматизированных моделей радиомикалов, прогнозирующих терапию (TR) и минимальную остаточную реакцию (MRD) в недавно диагностированном миеломе (MM) из базового МРТ. Ретроспективно, 118 Пациенты ММ из GMMG-HD7 судебное разбирательство (EudraCT: 2017-004768-37) с данными о TR и/или MRD после индуктивной терапии и базовой МРТ. Данные были разделены по центрам в комплект учебных материалов (центр 1-2; n = 79) и комплект испытаний (центр 3-10; n = 39). TR был классифицирован как очень хороший частичный ответ или лучше п

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… Relevant clinical parameter collected before treatment included patient’s age, sex, body mass index (BMI), M-protein, SFLC-ratio, beta2-microglobulin, calcium levels, creatinine, lactate dehydrogenase (LDH), serum albumin, serum total protein, hemoglobulin, PCI, major histocompatibility complex (MHC) … Histocompatibility Complex Type (n) | 50 (IgG)/17 (IgA)/1 (IgM)/10 (Light Chain)/1 (Biclonal) | 22 (IgG)/10 (IgA)/0 (IgM)/6 (Light Chain)/1 (Biclonal) Cytogenetics gain(1q) (n) | 28 | 10 del(17p) (n) | 10 | 2 t(4;14) (n) | 14 | 3 Prediction of therapy response Four models were trained for the prediction …

Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases.

The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor development. Regardless, it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses, thus allowing continuous tumor growth and development. Immune evasion has emerged as a significant factor contributing to the progression and immune resistance of pancreatic cancer. Compared with other cancers, pancreatic cancer has a tumor microenvironment that can resist most treatment modalities, including emerging immunotherapy. Sadly, the u

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… HDAC inhibitors can also increase the expression of major histocompatibility complex (MHC) and its costimulatory molecules leading to T-cell activation[ 48 ]. … These neoantigens are captured by antigen-presenting cells and present the antigens on the major histocompatibility complex to T cells (Step 3), allowing the T cells to be primed and activated. …

Tumour Immunotherapy and Applications of Immunological Products: A Review of Literature.

Malignant tumors, characterized by uncontrolled cell proliferation, are a leading global health challenge, responsible for over 9.7 million deaths in 2022, with new cases expected to rise to 35 million annually by 2050. Immunotherapy is preferred to other cancer therapies, offering precise targeting of malignant cells while simultaneously strengthening the immune system's complex responses. Advances in this novel field of science have been closely linked to a deeper knowledge of tumor biology, particularly the intricate interplay between tumor cells, the immune system, and the tumor microenvir

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… TAAs trigger T lymphocyte responses via the major histocompatibility complex (MHC) and can lead to the destruction of tumor cells through cytotoxicity mediated by CD8 cells and antibody-dependent complement activation [ 8 , 30 ]. … Upon recognition of TAAs presented by major histocompatibility complex class I (MHC-I) molecules on the tumor cell surface, CTLs are activated and exert their cytotoxic effects by releasing perforin and granzymes, which induce apoptosis in the target tumor cells [ 33 ]. …

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural

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… T cells recognize their target cells via their TCR, which has six distinct subunits and is among the most intricate receptor complexes in our body. 15 , 16 The TCRs of CD8+ and CD4+ T cells utilize their variant alpha and beta subunits to recognize specific peptide/major histocompatibility complexes … Augmented serum level of major histocompatibility complex class I-related chain a (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions . BMC Cancer . 2008 ; 8 ( 1 ): 16 . …

Breaking Boundaries: Immunotherapy for Myeloid Malignancies.

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of im

Microbiota-derived metabolites as modulators of cancer immunotherapy response.

The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to

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… MR1, major histocompatibility complex class I-related protein. MAIT, mucosal-associated invariant T cell. E. rectale , Eubacterium rectale . MAPK mitogen-activated protein kinase, DC dendritic cell, AhR aryl hydrocarbon receptor, GrzmB granzyme B, TMAO trimethylamine-N-oxide. Created in BioRender. … Moreover, another subset of innate-like T cells, MAIT cells, can recognise and be strongly activated by bacterial metabolites derived from riboflavin synthesis, such as 5-OP-RU (de novo production, Box 1 ), when presented by the major histocompatibility complex-related 1 (MR1) molecule 39 , 40 . …

Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis.

Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals

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… histocompatibility complex, class II invariant chain | 2.1 | 2.2 | 2.7 | None CFB | complement factor B | 4.4 | 2.8 | 3.8 | None Down | CEACAM1 | carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) | 0.2 | 0.4 | 0.4 | angiogenesis, cell adhesion, cell migration ExoCarta … histocompatibility complex, class II, DR alpha | 3.5 | 2.1 | 2.3 | adaptive immune response HLA-DRB1 | major histocompatibility complex, class II, DR beta 1 | 3.6 | 2.4 | 2.9 | adaptive immune response HP | haptoglobin | 3.3 | 9.0 | 2.7 | None IGKC | immunoglobulin kappa constant | 11.7 | 8.1 | 5.9 …

Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature.

The Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are enduring and well-known conditions. These disorders are characterized by the abnormal growth of one or more hematopoietic cell lineages in the body's stem cells, leading to the enlargement of organs and the manifestation of constitutional symptoms. Numerous studies have provided evidence indicating that the pathogenesis of these diseases involves the dysregulation of the immune system and the presence of chronic inflam

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… Consequently, LAG-3 can bind to major histocompatibility complex (MHC) class II molecules, albeit at a distinct site, with even greater affinity than CD4 [ 41 ]. … Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc. Natl. Acad. Sci. USA. 1997;94:5744–5749. doi: 10.1073/pnas.94.11.5744. 42. Hannier S., Triebel F. …

Spontaneous remission in diffuse large cell lymphoma: a case report.

BackgroundSpontaneous remission in solid malignancies has been documented. However, spontaneous remission in aggressive diffuse large b cell lymphoma is exceedingly rare. Previous reports of lymphoma remission suggest that not yet fully characterized tumor-intrinsic and microenvironment mechanisms cooperate with spontaneous regression.Case descriptionHere, we report the case of an 88-year-old white woman with diffuse large b cell lymphoma (follicular lymphoma transformed) who achieved morphologic spontaneous remission 3 months after her diagnostic core biopsy. We examined 16 similar cases of d

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… In the same patient, the CD4/CD8 DP population retained major histocompatibility complex (MHC) class I restricted activity against autologous tumor cells [ 21 ]. … Abbreviations activated B-cell Cell of origin Computed tomography Cytotoxic T cell Diffuse large b cell lymphoma Double positive Epstein–Barr virus Human leukocyte antigen-antigen D related Idiopathic pulmonary fibrosis Major histocompatibility complex Non-Hodgkin lymphoma Natural killer …

Upregulation of β2-microglobulin expression in progressive human oral squamous cell carcinoma.

The aim of the present study was to investigate β2-microglobulin (β2-M) expression in normal oral mucosa and progressive oral squamous cell carcinoma (OSCC) and to assess the clinical significance of β2-microglobulin expression. The study included 10 cases of normal oral mucosa epithelium specimens, 55 cases of primary OSCC specimens, and 25 cases of OSCC metastasis specimens. Immunohistochemistry was used to determine β2-M expression, and its correlation with clinicopathological factors in progressive OSCC was evaluated. Immunohistochemistry showed that strong β2-M expression was significantl

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… It is present on the surface of all nucleated cells except for red blood cells ( 6 ). β2-M forms the β chain of the major histocompatibility complex (MHC) class I molecule [also known as human leukocyte antigens (HLAs) in humans] and has a 7-stranded β-pleated structure, which is believed to function … Abbreviations oral squamous cell carcinoma major histocompatibility complex human leukocyte antigens natural killer human immortalized oral epithelial cells References 1. Imai T, Toyota M, Suzuki H, et al. Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. …

Towards Novel Gene and Cell Therapy Approaches for Cervical Cancer.

Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases,

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… CARs can be directed against tumor-associated antigens and lead to an activation of the respective immune cells upon binding to the targeted antigen in a major histocompatibility complex (MHC)-independent manner. (iv) Modification of T cells with tumor-specific TCR. … Licensing of natural killer cells by self-major histocompatibility complex class I Immunol. Rev. 2006 214 143 154 10.1111/j.1600-065X.2006.00458.x 17100882 107. Wang W. Erbe A.K. Hank J.A. Morris Z.S. Sondel P.M. …