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#Naturalkiller cell-derived #exosome-based #cancertherapy: from biological roles to clinical significance and implications Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport. At the same time, natural killer cell-derived exosomes are easy to modify, and the engineered exosomes can be used in combination with a variety of current cancer therapies, which not only enhances the therapeutic efficacy, but also significantly reduces the side effects Natural killer (NK) cells originate from common lymphoid progenitors and can be obtained from sources like peripheral blood, cord blood, pluripotent stem cells, and NK cell lines. Over the years, several NK cell lines, such as NK92 and HANK1, have been established for cancer immunotherapy due to their therapeutic potential. NK cells are divided into two main subpopulations based on CD56 expression: CD56bright, which is cytokine-producing, and CD56dim, which is more cytotoxic. These cells develop in the bone marrow and other lymphoid organs, and can be classified into classical or tissue-resident NK cells. NK cell differentiation depends on the expression of receptors such as CD16 and CD57, and their activation relies on ligand/receptor interactions, balancing inhibitory and activating signals. NK cells are activated when tumor cells downregulate MHC I and upregulate NK cell-activating ligands, making them prime targets for cancer immunotherapy. Initially, NK cell-based therapies were used in hematopoietic stem cell transplants (HSCTs), where they provided graft-versus-leukemia effects without causing graft-versus-host disease. Subsequent studies demonstrated NK cell efficacy in non-transplant settings, leading to the development of Chimeric Antigen Receptor (CAR)-NK cells as an alternative to CAR-T therapies. With advancements in genetic engineering and a deeper understanding of NK cell biology, NK-based immunotherapies are becoming increasingly promising. Future innovations may also include NK cell-derived exosomes for cancer treatment Image: Origin of natural killer cell and cancer immunotherapy.  a) The origin of natural killer cells b) Localization of NK cells c) Natural killer cells function selectively d) Four ways natural killer cells fight tumors e) Natural killer cell-based therapies Source: https://lnkd.in/eNtSCAEj

La publicación revisa el papel de los metabolitos de la microbiota intestinal en la inmunoterapia contra tumores, centrándose en el bloqueo de HLA-E y NKG2A. Se destaca cómo metabolitos como los ácidos grasos de cadena corta, los derivados del triptófano y los ácidos biliares pueden modular la respuesta inmune, mejorando la eficacia de tratamientos como los anticuerpos anti-PD-1 y anti-CTLA-4. Estos hallazgos sugieren que la manipulación de la microbiota intestinal, a través de estrategias como la administración de probióticos y prebióticos, podría ofrecer nuevas perspectivas para optimizar la inmunoterapia personalizada en pacientes con cáncer.Dr. Alexander Ariel Padrón GonzálezDr. Jose Manuel Cervera Grau Jose G. Easy IMMUNO-ATMPs Rocket ProgramiCCS (iOncoCare) International Cancer Care Support

#Naturalkiller #cancerimmunotherapy Natural killer cell memory: challenges and opportunities for cancer immunotherapy Natural killer (NK) cells have been found to acquire immunological memory in a manner akin to T and B cells. The fundamental principles derived from the investigation of NK cell memory offer novel insights into innate immunity and have the potential to pave the way for innovative strategies to enhance therapeutic interventions against multiple diseases including cancer Research into NK cell memory responses has highlighted their potential in cancer treatment, particularly due to their ability to rapidly respond to previously encountered threats without needing antigen-specific receptors. Unlike T and B cells, NK cells utilize ‘innate memory’ for quicker, robust reactions, which can be enhanced when combined with other immunotherapies like CAR-engineered NK cells. These cells show promise in treating hematologic malignancies and, when paired with radiotherapy, could improve immune infiltration in solid tumors. Synergistic approaches, such as using IL-2-activated NK cells with anti-PD-L1 antibodies, have shown potential in reshaping the tumor environment to enhance immunotherapy effectiveness. As NK cell memory research advances, including studies on cytokine-driven NK cells and human CMV adaptive NK cells, it could lead to innovative strategies for cancer treatment. In the image:  The application of memory NK cells in cancer immunotherapy. a. The cytokine IL-12/15/18 induces the generation of memory NK cells, and enhancing the secretion of IFNγ, perforin, and granzymes for effective eradication of cancer cells. b. Memory NK cells induced by IL-12/15/18 can be transduced with CARs, thereby enhancing their antineoplastic activity. c. The administration of antibodies such as cetuximab, rituximab, and AFM13 has been shown to augment the antitumor efficacy in memory NK cells Source: https://lnkd.in/ety_aubU

#B1cells #cancer

#Bcells #immunecheckpoint #solidtumors B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets of patients and is now the standard of care in several solid tumor types. Most studies have focused on T cell engagement and response, but there is a growing evidence that B cells may be key players in the establishment of an organized immune response, notably through tertiary lymphoid structures. Mechanisms of B cell response include antibody-dependent cellular cytotoxicity and phagocytosis, promotion of CD4+ and CD8+ T cell activation, maintenance of antitumor immune memory. In several solid tumor types, higher levels of B cells, specific B cell subpopulations, or the presence of tertiary lymphoid structures have been associated with improved outcomes on immune checkpoint inhibitors. The fate of B cell subpopulations may be widely influenced by the cytokine milieu, with versatile roles for B-specific cytokines B cell activating factor and B cell attracting chemokine-1/CXCL13, and a master regulatory role for IL-10. Roles of B cell-specific immune checkpoints such as TIM-1 are emerging and could represent potential therapeutic targets. Image:  BCR in solid tumors.  A) Coordination of the antitumor immune response by B cells. Antigen recognition by the B-cell receptor triggers a T cell-dependent or T cell-independent B cell response. The T cell-dependent response involves B and T-cell crosstalks within secondary or tertiary lymphoid structures. Interactions between B-cells and TFh through the CD40/CD40L axis allows for TFh activation, as well as initiation of a B cell germinal center reaction. Activation of TFh cells promotes T CD8+ activation and expansion in the T cell zone, ultimately prompting efficient T cell-mediated cytotoxicity. The germinal center reaction involves a positive selection of high-affinity, class-switched B cells that will differentiate into long-lived switched (IgG+) memory B cells or IgG+plasma cells. The humoral response exert antitumor effects through antibody-dependent cytotoxicity and phagocytosis. B) Modulation of the immune response by B cells. Tumor infiltration by regulatory B cells secreting immunosuppressive cytokines such as IL-10 allows for an immunosuppressive microenvironment. Immune complexes involving immunoglobulins and tumor antigens may promote activation of myeloid-derived suppressor cells. Complement activation by immunoglobulins may also promote MDSC activation and angiogenesis, inducing a protumoral microenvironment. Source:https://lnkd.in/e6bX6aM8

La publicación aborda los probióticos de nueva generación (NGP), destacando su evolución desde los probióticos convencionales hasta su papel en la prevención y tratamiento de enfermedades específicas relacionadas con la disbiosis, como la colitis, obesidad y diabetes. A través de avances científicos, como la secuenciación de próxima generación, se ha identificado un grupo de bacterias con funciones clave en la salud intestinal y el equilibrio inmunológico. Además, se analiza el interés comercial y las regulaciones necesarias para su aplicación en productos farmacéuticos, posicionando a los NGP como una prometedora herramienta en la medicina personalizada.Dr. Alexander Ariel Padrón González Dr. Alexander Ariel Padrón González Easy IMMUNO-ATMPs Rocket Program

Comunicar Ciencia, Inspirar Generaciones: Hacia una Sociedad Más Informada 

#Bcell #Tcell #autoimmunedisease #CARTcelltherapy Disrupting B and T-cell collaboration in autoimmune disease: T-cell engagers versus CAR T-cell therapy? B and T cells collaborate to drive autoimmune disease (AID). Historically, B- and T-cell (B–T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B-cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab, or ofatumumab. Refractory AID is a significant problem for patients with incomplete BCD with a greater frequency of IgD−CD27+ switched memory B cells, CD19+CD20− B cells, and plasma cells that are not directly targeted by anti-CD20 antibodies, whereas most lymphoid tissue plasma cells express CD19. Furthermore, B–T-cell collaboration is predominant in lymphoid tissues and at sites of inflammation such as the joint and kidney, where BCD may be inefficient, due to limited access to key effector cells. In the treatment of cancer, chimeric antigen receptor (CAR) T-cell therapy and T-cell engagers (TCE) that recruit T cells to induce B-cell cytotoxicity have delivered promising results for anti-CD19 CAR T-cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab, or epcoritamab. Limited evidence suggests that anti-CD19 CAR T-cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. This graphical abstract compares the hypothetical timelines of CD19 CAR T-cell therapy (green line) and CD19-TCE (purple line) in the context of autoimmune disease flare. CAR T-cell therapy is often limited to specialized centers due to its high-production costs, labor-intensive process, delayed effector T-cell pool establishment, and tolerability issues with prerequisite toxic lymphodepleting chemotherapy, potentially restricting its use and impacting patient outcomes. In contrast, CD19-TCB, readily available and immediately deployable upon disease flare detection, mitigates the risks associated with disease progression due to delays in CAR T-cell therapy access. Source: https://lnkd.in/ebFymrrY

La publicación explora la conexión entre las bacterias orales y la enfermedad inflamatoria intestinal (EII), destacando cómo la disbiosis oral y la colonización ectópica de microorganismos orales pueden exacerbar la inflamación intestinal. Se evidencia que los pacientes con EII presentan alteraciones en su microbioma oral, lo que se relaciona con manifestaciones clínicas y actividad de la enfermedad. Además, se sugiere que la salud bucal puede servir como un indicador de la EII y que un enfoque multidisciplinario en el tratamiento, que incluya la evaluación del microbioma oral, podría mejorar los resultados clínicos. Esta investigación subraya la importancia de considerar la salud oral como parte integral del manejo de la EII.Dr. Jose Manuel Cervera GrauDr. Alexander Ariel Padrón GonzálezPegah ShakibniaEasy IMMUNO-ATMPsRocket Program

Los subproductos del caqui, como las cáscaras y el orujo, están demostrando ser una fuente rica en fibra y compuestos antioxidantes que promueven la salud intestinal y reducen la inflamación. Estos hallazgos abren nuevas oportunidades para la industria alimentaria, permitiendo la creación de ingredientes funcionales que no solo mejoran la salud humana, sino que también apoyan la sostenibilidad al reducir el desperdicio. Transformar lo que antes se consideraba "desperdicio" en recursos valiosos es un paso clave hacia un futuro más saludable y sostenible.Dr. Jose Manuel Cervera GrauDr. Alexander Ariel Padrón González Pegah Shakibnia Rocket Program Easy IMMUNO-ATMPs