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Потенциал новых методов лечения BCMA для преодоления сопротивления в множестве миеломы.

Внутриклеточных антигенов является важной терапевтической целью в множестве миеломы. Ряд продуктов химерика антигенного рецептора Т-клеток (CAR-T), биконкретных Т-клеток и антителных пар, предназначенных для BCMA, утверждаются на случай рецидива/реактивного заболевания. После длительного воздействия двух специфичных свойств доминирующим механизмом является отказ от антигенной деятельности, включая биаллеловую потерю TNFRSF17, непереносимые мутации в внеклеточном доме BCMA, пропуск через секретазу и регулирование транскрипции. Т-внутренняя дисфункция, характеризующаяся истощением, трогоцитозом

Совпадение в аннотации оригинала
IntroductionB-cell maturation antigen is an important therapeutic target in multiple myeloma. Several chimeric antigen receptor T-cell (CAR- … after prolonged exposure to bispecifics. T-cell-intrinsic dysfunction, characterized by exhaustion, trogocytosis, and impaired fitness, is a key driver of relapse after CAR-T therapy. Tumor-intrinsic genomic complexity and plasma cell identity escape, a recently described state of highly proliferative, lineage-divergent plasma cells with downregulation of BCMA …

Structural basis for carbohydrate recognition by the Gal/GalNAc lectin of Entamoeba histolytica involved in host cell adhesion.

Intestinal amoebiasis is caused by Entamoeba histolytica, one of the deadliest human-infective parasites. Central to its pathogenicity is its binding to mucosal carbohydrates, which precedes tissue damage by trogocytosis. Carbohydrate binding is mediated by a single adhesin, the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin, which is the leading vaccine candidate for amoebiasis. We present the structure of the native heterodimeric lectin, revealing an ordered core containing the light chain and the N-terminal region of the heavy chain. Structures obtained in the presence of ligand show t…

Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling.

Macrophages and dendritic cells acquire bacteria and cytosolic content from other cells without killing the donor cell through a trogocytosis-associated process termed merocytophagy. While characteristics of this behavior have been partially identified, the mechanism and potential contribution to the response to infection are unclear. Here, we reveal that a wide range of distinct species of bacteria stimulate enhanced merocytophagy in macrophages through pattern recognition receptor (PRR). Further, we found that cell-to-cell transfer in response to Francisella tularensis infection occurs in a …

The Perils and Promise of Cellular Cannibalism in Development, Homeostasis, and Disease.

Cellular cannibalism, defined as one cell eating another, is a widespread cellular behavior in organisms ranging from flies and worms to fish and mammals, where it is essential for development and homeostasis. Some cells nibble on other cells in a process called trogocytosis or grooming. Alternatively, cells can engulf other cells whole, as when macrophages consume stressed stem cells or aged red blood cells. Excessive cellular cannibalism can lead to degenerative disease or immunodeficiency, and cancer cells can hijack this normal behavior to fuel their growth and evade immune attack. Next-ge…

Neutrophils in the female reproductive tract: immune interactions and sperm adaptations.

Human fertilization is a coordinated process involving interaction of sperm with the oocyte. As the sperm pass through the female reproductive tract (FRT), they are presented with numerous challenges. These include navigating through highly viscous cervical mucus while evading immune responses to successfully fertilize the oocyte. The female immune system facilitates sperm selection while providing protection against pathogens. Neutrophils, a major component of the innate immune system, use mechanisms such as phagocytosis, neutrophil extracellular trap formation, and trogocytosis to play a cru…

Targeting PD-1+ T cells with chimeric antigen receptors to reduce the HIV reservoir.

The unique ability of chimeric antigen receptor (CAR) T cells to infiltrate tissues is revolutionizing our perspectives for tackling severe, … onblocking (nbPD1-CAR) anti-PD-1 monoclonal antibody. The CAR avidity modulated T cell sensitivity, trogocytosis, and effector functions, independently of the PD-1 signaling domain. Both anti-PD-1 CAR-T cells could persist for 70 days in HIV-infected humanized mice, correlating with viral protection and a disruption of the lymphoid architecture in the white pu …

Mechanistic and Clinical Differences Between Daratumumab and Isatuximab in Multiple Myeloma: Emerging Roles of 1q Gain and Immune Remodeling.

Anti-CD38 monoclonal antibodies have substantially improved outcomes in multiple myeloma (MM). Although daratumumab and isatuximab target th … q21 amplification. In contrast, daratumumab exerts prominent Fc-dependent immune effects, including trogocytosis-mediated downregulation of CD38 and VLA-4, suppression of cell adhesion-mediated drug resistance, and modulation of the immune microenvironment, potentially enhancing subsequent T-cell-redirecting therapies. We further discuss the relevance of these …

Macrophages tune NK cell IFNγ production through direct lipid transfer.

Natural killer (NK) cells are critical effectors of innate immunity, but their activity is strongly influenced by metabolic state. While int … macrophages to NK cells requires cell-cell contact and is associated with CD36 protein transfer via trogocytosis. Blocking fatty acid synthesis specifically in macrophages prevents lipid accumulation in NK cells and restores both mTORC1 activity and IFNγ production. These findings define a previously unrecognized mechanism of macrophage-NK cell cross-regulatio …

T-B interactions yield CD3+ B cells and CD20+ T cells with pathogenic features in multiple sclerosis.

Classically, B and T cells are differentiated by their mutually exclusive expression of surface markers such as CD3 and CD20, but it is now … r T (Tfh) cells displayed CD20. In vitro, coactivation of T and B cells induced marker exchange via trogocytosis. We refer to the resulting cells as "masquerading" lymphocytes and analyzed them in multiple sclerosis (MS). CD20+ T cells were markedly enriched in cerebrospinal fluid, exhibited cytotoxic gene signatures, accumulated in perivascular inflammatory c …

Resistance to BCMA-Directed CAR T-Cell Therapy in Multiple Myeloma: Biology, Clinical Patterns, and Strategies to Overcome Treatment Failure.

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for heavily pretreated multiple myeloma, achieving unprecedented response rates in patients with otherwise dismal outcomes. However, the vast majority of patients eventually relapse due to complex resistance mechanisms. These include antigen-dependent escape-such as loss of the BCMA target through genetic deletion, epitope-level mutation, or antigen downregulation via shedding and trogocytosis-as well as antigen-independent tumor adaptations like clonal evolution and lineage pl…

B cell CD19 is transferred between immune cells in mice and humans.

When immune cells interact, they frequently exchange membrane-bound antigens. Our evolving understanding of these processes challenges the cellular specificity of lineage markers and therapeutic monoclonal antibodies. By using mouse and human B-T cell co-cultures, we report that CD19, an assumingly exclusive B cell marker, is transferred via trogocytosis when B cells activate T cells. In a B cell-driven model of experimental autoimmune encephalomyelitis, CD19+ T cells expand and show enhanced features of activation, differentiation, and encephalitogenic potential ex vivo. Additionally, co-tran…

Expression and functional role of HLA-G in immune cells from patients with systemic lupus erythematosus.

Human leukocyte antigen (HLA)-G is a class I non-classical HLA molecule with an important regulatory role on the immune response. The possib … phocytes. Finally, lymphocytes from SLE patients tended to display a lower acquisition of HLA-G (by trogocytosis) from autologous monocytes compared to controls. Our results might have implications for the immune abnormalities observed in patients with SLE.

Endocytosis at the maternal-fetal interface: balancing nutrient transport and pathogen defense.

Endocytosis represents a category of regulated active transport mechanisms. These encompass clathrin-dependent and -independent mechanisms, … restriction of potentially harmful chemicals and drugs to allow fetal development. In this context, trogocytosis, a specific form of endocytosis, plays a crucial role in immunological tolerance and infection prevention. Endocytosis is also thought to play a significant role in nutrient and toxin handling at the maternal-fetal interface, though its mechanisms r …

CD30 Expression and Its Functions during the Disease Progression of Adult T-Cell Leukemia/Lymphoma.

CD30, a member of the tumor necrosis factor receptor superfamily, plays roles in pro-survival signal induction and cell proliferation in per … findings have revealed super-enhancer-mediated overexpression at the CD30 locus, CD30 signaling via trogocytosis, and CD30 signaling-induced lymphomagenesis in vivo. Successful anti-CD30 antibody-drug conjugate (ADC) therapy for HL, ALCL, and PTCL supports the biological significance of CD30 in these lymphomas. In this review, we discuss the roles of CD30 over …

Tumor Acidosis Boosts Antibody-Driven Cytotoxic Potential of Neutrophils.

The acidic tumor microenvironment (pH 6.3-7.1) influences immune cell function, yet its impact on antibody-mediated killing remains poorly u … MCs had a varying impact. This increased neutrophil activity was accompanied by elevated IgA-driven trogocytosis, while protumor reactive oxygen species production and neutrophil extracellular trap (NET) formation were suppressed. Cytokine profiling and Western blot analysis revealed increased Leukotriene B4 (LTB4) secretion and extracellular signal-regulated …

Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering.

The recent advancements in cancer immunotherapy have spotlighted the potential of natural killer (NK) cells, particularly chimeric antigen r … hes for CAR-NK cell generation are becoming increasingly essential. Cutting-edge techniques such as trogocytosis, electroporation, lipid nanoparticle (LNP) delivery, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) gene editing and transposons not only enhance the efficiency and safety of CAR-NK cell engineering but …

Mechanisms Driving Neutrophil-Induced T-cell Immunoparalysis in Ovarian Cancer.

T-cell activation and expansion in the tumor microenvironment (TME) are critical for antitumor immunity. Neutrophils in the TME acquire a co … uppression of tumor-associated lymphocytes. ASC-activated neutrophils adhered to T cells and caused trogocytosis of T-cell membranes. These injury and signaling cues resulted in T-cell immunoparalysis characterized by impaired NFAT translocation, IL2 production, glucose uptake, mitochondrial function, and mTOR activation. Our results demonstrate that complemen …

Research progress of targeted BCMA CAR-T therapy for relapsed/refractory multiple myeloma antigen-negative relapse.

Chimeric antigen receptor T cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has emerged as a novel and effective modality fo … ncluding diminished or lost tumor antigen expression, BCMA shedding, impaired antigen presentation, trogocytosis, antigen mutations, and alternative splicing. To overcome the problem of antigen-negative relapse in BCMA CAR-T therapy, a variety of strategies are being explored. These include dual/multi-specific CAR-T cell therapy, combination therapies with ant …

Neutrophil interactions with the sexually transmitted parasite Trichomonas vaginalis: implications for immunity and pathogenesis.

Trichomoniasis is the third most common sexually transmitted infection in humans and is caused by the protozoan parasite, Trichomonas vagina … lling. In vitro, the parasite is killed by neutrophils using a novel antimicrobial mechanism called trogocytosis, which probably involves both innate and adaptive immunity. While mechanisms of evasion are mostly conjecture at present, the persistence of Tv infections in patients argues strongly for their existence. Additionally, many strains of Tv harbour micr …

Monocyte-mediated metabolic rewiring via CD31-CD38 interactions promotes growth and drug-resistance in multiple myeloma.

Multiple myeloma (MM) cells interact with different components of the bone marrow (BM) microenvironment, which plays a critical role in MM p … monocytes acquired a divergent role and obtained mitochondria from MM cells through the process of trogocytosis. Daratumumab-mediated disruption of mitochondrial transfer reduced the mitochondrial content in MM cells, prevented the boost in OXPHOS, significantly impaired MM cell growth and migration, and mitigated drug-resistance. In conclusion, we reveal a c …