Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma
| العنوان: | Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma |
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| المؤلفون: | Nadia Plantier, Sabrina A. Hogan, Simone M. Goldinger, Marieke I.G. Raaijmakers, Anais Courtier, Jean-François Mouret, Thi Dan Linh Nguyen-Kim, Phil F. Cheng, John B. A. G. Haanen, Mitchell P. Levesque, Solène Perez, Pia Kvistborg, Reinhard Dummer, Nicoletta F Jaberg-Bentele, Manuarii Manuel, Nicolas Pasqual |
| المساهمون: | University of Zurich, Levesque, Mitchell P |
| المصدر: | Cancer Immunology Research |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Immunology, Receptors, Antigen, T-Cell, 610 Medicine & health, chemical and pharmacologic phenomena, Antibodies, Monoclonal, Humanized, Peripheral blood mononuclear cell, 03 medical and health sciences, symbols.namesake, Antineoplastic Agents, Immunological, 0302 clinical medicine, Internal medicine, medicine, Humans, CTLA-4 Antigen, 1306 Cancer Research, Progression-free survival, Melanoma, Fisher's exact test, Aged, 2403 Immunology, Receiver operating characteristic, 10042 Clinic for Diagnostic and Interventional Radiology, business.industry, T-cell receptor, 10177 Dermatology Clinic, Immunotherapy, Middle Aged, medicine.disease, Ipilimumab, Progression-Free Survival, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Monoclonal, symbols, Female, business |
| الوصف: | Many metastatic melanoma patients experience durable responses to anti-PD1 and/or anti-CTLA4; however, a significant proportion (over 50%) do not benefit from the therapies. In this study, we sought to assess pretreatment liquid biopsies for biomarkers that may correlate with response to checkpoint blockade. We measured the combinatorial diversity evenness of the T-cell receptor (TCR) repertoire (the DE50, with low values corresponding to more clonality and lack of TCR diversity) in pretreatment peripheral blood mononuclear cells from melanoma patients treated with anti-CTLA4 (n = 42) or anti-PD1 (n = 38) using a multi-N-plex PCR assay on genomic DNA (gDNA). A receiver operating characteristic curve determined the optimal threshold for a dichotomized analysis according to objective responses as defined by RECIST1.1. Correlations between treatment outcome, clinical variables, and DE50 were assessed in multivariate regression models and confirmed with Fisher exact tests. In samples obtained prior to treatment initiation, we showed that low DE50 values were predictive of a longer progression-free survival and good responses to PD-1 blockade, but, on the other hand, predicted a poor response to CTLA4 inhibition. Multivariate logistic regression models identified DE50 as the only independent predictive factor for response to anti-CTLA4 therapy (P = 0.03) and anti-PD1 therapy (P = 0.001). Fisher exact tests confirmed the association of low DE50 with response in the anti-CTLA4 (P = 0.041) and the anti-PD1 cohort (P = 0.0016). Thus, the evaluation of basal TCR repertoire diversity in peripheral blood, using a PCR-based method, could help predict responses to anti-PD1 and anti-CTLA4 therapies. |
| وصف الملف: | Peripheral_blood_TCR_repertoire_profiling_may_facilitate.pdf - application/pdf |
| تدمد: | 2326-6074 2326-6066 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2183a0c56e9ee4715bc5ea53f32f0b44Test https://doi.org/10.1158/2326-6066.cir-18-0136Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2183a0c56e9ee4715bc5ea53f32f0b44 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23266074 23266066 |
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