cad a22 4500 551414456 20200601065752.0 cr unu---uuuuu 181214e20190101xx s 000 0 eng 10.5167/uzh-159305 doi 10.1158/2326-6066.CIR-18-0136 doi (ZORA)oai:www.zora.uzh.ch:159305 610 ddc 30425105 pmid Peripheral blood TCR repertoire profiling may facilitate patient stratification for immunotherapy against melanoma [Elektronische Daten] [Sabrina A Hogan, Anaïs Courtier, Phil F Cheng, Nicoletta F Jaberg-Bentele, Simone M Goldinger, Manuarii Manuel, Solène Perez, Nadia Plantier, Jean-François Mouret, Thi Dan Linh Nguyen-Kim, Marieke I G Raaijmakers, Pia Kvistborg, Nicolas Pasqual, John B A G Haanen, Reinhard Dummer, Mitchell P Levesque] openAccess eu-repo 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 liquid biopsies 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 ROC 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 responses 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. Clinic for Diagnostic and Interventional Radiology zora Dermatology Clinic zora Hogan Sabrina A. joint author Courtier Anaïs joint author Cheng Phil F. joint author Jaberg-Bentele Nicoletta F. joint author Goldinger Simone M. joint author Manuel Manuarii joint author Perez Solène joint author Plantier Nadia joint author Mouret Jean-François joint author Nguyen-Kim Thi Dan Linh joint author Raaijmakers Marieke I G. joint author Kvistborg Pia joint author Pasqual Nicolas joint author Haanen John B A G. joint author Dummer Reinhard joint author Levesque Mitchell P. joint author Cancer Immunology Research 7(1):77-85 https://www.zora.uzh.ch/id/eprint/159305/1/Peripheral_blood_TCR_repertoire_profiling_may_facilitate.pdf text/html WWW-Backlink auf das Repository BK010053 XK010053 XK010000 1 Journal Article PeerReviewed zora EC/H2020/641458 zora grantAgreement ZORA ZORA ZORA Journal Article openAccess ZORA 856 40 https://www.zora.uzh.ch/id/eprint/159305/1/Peripheral_blood_TCR_repertoire_profiling_may_facilitate.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Hogan Sabrina A. joint author ZORA 700 1- Courtier Anaïs joint author ZORA 700 1- Cheng Phil F. joint author ZORA 700 1- Jaberg-Bentele Nicoletta F. joint author ZORA 700 1- Goldinger Simone M. joint author ZORA 700 1- Manuel Manuarii joint author ZORA 700 1- Perez Solène joint author ZORA 700 1- Plantier Nadia joint author ZORA 700 1- Mouret Jean-François joint author ZORA 700 1- Nguyen-Kim Thi Dan Linh joint author ZORA 700 1- Raaijmakers Marieke I G. joint author ZORA 700 1- Kvistborg Pia joint author ZORA 700 1- Pasqual Nicolas joint author ZORA 700 1- Haanen John B A G. joint author ZORA 700 1- Dummer Reinhard joint author ZORA 700 1- Levesque Mitchell P. joint author ZORA 773 0- Cancer Immunology Research 7(1):77-85