مؤتمر
أعرض في EDS

T CELL IMMUNOTHERAPIES TRIGGER NEUTROPHIL ACTIVATION TO ELIMINATE TUMOR ANTIGEN ESCAPE VARIANTS

التفاصيل البيبلوغرافية
العنوان: T CELL IMMUNOTHERAPIES TRIGGER NEUTROPHIL ACTIVATION TO ELIMINATE TUMOR ANTIGEN ESCAPE VARIANTS
المؤلفون: Hirschhorn, Daniel, Budhu, Sadna, Schroder, David, Kraehenbuehl, Lukas, Flammar, Anne-Laurent, Chow, Andrew, Schulze, Isabell, Schad, Sara, Ricca, Jacob, Gasmi, Billel, De Henau, Olivier, Mangarin, Levi, Redmond, David, Cortez, Czrina, Liu, Cailian, Holland, Aliya, Gigoux, Mathieu, Arora, Asrhi, Panageas, Katherine, Rizzuto, Gabrielle, Albrengues, Jean, Egeblad, Mikala, Wolchok, Jedd, Merghoub, Taha
بيانات النشر: BMJ
سنة النشر: 2021
المجموعة: Cold Spring Harbor Laboratory: CSHL Institutional Repository
مصطلحات موضوعية: Neutrophil extracellular traps, melanomas, neutrophils
الوصف: BackgroundTargeted immune-based therapies such as adoptive T cell transfer (ACT) are often ineffective because tumors evolve over time and under selective pressure display antigen loss variant clones. A classic example in melanoma is de-differentiation and loss of expression of antigenic proteins. Therapies that activate multiple branches of the immune system may eliminate such escape variantsMethodsHere we show that melanoma-specific CD4+ ACT therapy in combination with OX40 co-stimulation or CTLA-4 blockade can eradicate large melanoma tumors with clonal escape variants.ResultsEarly on-target recognition of melanoma antigens by adoptively transferred tumor-specific CD4+ T cells was required. Surprisingly, however, complete tumor eradication was partially dependent on neutrophils. Supporting these findings, extensive neutrophil activation and neutrophil extracellular traps were found in mouse tumors and in biopsies of melanoma patients treated with immune checkpoint blockade.ConclusionsOur findings uncover a novel interplay between T cells mediating the initial tumor- and tissue-specific immune response, and neutrophils mediating tumor destruction of antigen loss variants.Ethics ApprovalAll tissues were collected at MSKCC following study protocol approval by the MSKCC Institutional Review Board. All mouse procedures were performed in accordance with institutional protocol guidelines at Memorial Sloan-Kettering Cancer Center (MSKCC) under an approved protocol.
نوع الوثيقة: conference object
اللغة: unknown
العلاقة: Hirschhorn, Daniel, Budhu, Sadna, Schroder, David, Kraehenbuehl, Lukas, Flammar, Anne-Laurent, Chow, Andrew, Schulze, Isabell, Schad, Sara, Ricca, Jacob, Gasmi, Billel, De Henau, Olivier, Mangarin, Levi, Redmond, David, Cortez, Czrina, Liu, Cailian, Holland, Aliya, Gigoux, Mathieu, Arora, Asrhi, Panageas, Katherine, Rizzuto, Gabrielle, Albrengues, Jean, Egeblad, Mikala, Wolchok, Jedd, Merghoub, Taha (November 2021) T CELL IMMUNOTHERAPIES TRIGGER NEUTROPHIL ACTIVATION TO ELIMINATE TUMOR ANTIGEN ESCAPE VARIANTS. In: SITC 36th Anniversary Annual Meeting (SITC 2021).
DOI: 10.1136/jitc-2021-SITC2021.099
الإتاحة: https://doi.org/10.1136/jitc-2021-SITC2021.099Test
http://repository.cshl.edu/id/eprint/40592Test/
رقم الانضمام: edsbas.85EF1201
قاعدة البيانات: BASE
الوصف
DOI:10.1136/jitc-2021-SITC2021.099