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Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

التفاصيل البيبلوغرافية
العنوان: Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.
المؤلفون: Au, Lewis, Hatipoglu, Emine, Robert de Massy, Marc, Litchfield, Kevin, Beattie, Gordon, Rowan, Andrew, Schnidrig, Desiree, Thompson, Rachael, Byrne, Fiona, Horswell, Stuart, Fotiadis, Nicos, Hazell, Steve, Nicol, David, Shepherd, Scott TC, Fendler, Annika, Mason, Robert, Del Rosario, Lyra, Edmonds, Kim, Lingard, Karla, Sarker, Sarah, Mangwende, Mary, Carlyle, Eleanor, Attig, Jan, Joshi, Kroopa, Uddin, Imran, Becker, Pablo D, Sunderland, Mariana Werner, Akarca, Ayse, Puccio, Ignazio, Yang, William W, Lund, Tom, Dhillon, Kim, Vasquez, Marcos Duran, Ghorani, Ehsan, Xu, Hang, Spencer, Charlotte, López, José I, Green, Anna, Mahadeva, Ula, Borg, Elaine, Mitchison, Miriam, Moore, David A, Proctor, Ian, Falzon, Mary, Pickering, Lisa, Furness, Andrew JS, Reading, James L, Salgado, Roberto, Marafioti, Teresa, Jamal-Hanjani, Mariam, PEACE Consortium, Kassiotis, George, Chain, Benny, Larkin, James, Swanton, Charles, Quezada, Sergio A, Turajlic, Samra, TRACERx Renal Consortium
بيانات النشر: Elsevier BV
//dx.doi.org/10.1016/j.ccell.2021.10.001
Cancer Cell
سنة النشر: 2021
المجموعة: Apollo - University of Cambridge Repository
مصطلحات موضوعية: T cell receptor, TCR clonal maintenance, TCR clonal replacement, anti-PD-1, autopsy, clear cell renal cell carcinoma, human endogenous retrovirus, multiregion, nivolumab, CD8-Positive T-Lymphocytes, Carcinoma, Renal Cell, Clinical Trials, Phase II as Topic, Drug Resistance, Neoplasm, Endogenous Retroviruses, Gene Expression Profiling, Genomics, Humans, Immune Checkpoint Inhibitors, Kidney Neoplasms, Prospective Studies, Receptors, Antigen, T-Cell, Sequence Analysis, RNA, Single-Cell Analysis, Tumor Escape
الوصف: ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: https://www.repository.cam.ac.uk/handle/1810/330209Test
DOI: 10.17863/CAM.77651
الإتاحة: https://doi.org/10.17863/CAM.77651Test
https://www.repository.cam.ac.uk/handle/1810/330209Test
حقوق: Attribution-NonCommercial-NoDerivatives 4.0 International ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/
رقم الانضمام: edsbas.E6C1AF73
قاعدة البيانات: BASE
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