Yoshiro Nakahara1,2, Takaji Matsutani3, Yuka Igarashi4, Norikazu Matsuo5, Hidetomo Himuro4,6, Haruhiro Saito1, Kouzo Yamada1, Kenta Murotani7, Tomoaki Hoshino5, Koichi Azuma5, Tetsuro Sasada8,9. 1. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. 2. Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. 3. Repertoire Genesis, Inc, Ibaraki, Osaka, Japan. 4. Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, Japan. 5. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. 6. Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan. 7. Biostatistics Center, Kurume University, Kurume, Fukuoka, Japan. 8. Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, Japan. tsasada@kcch.jp. 9. Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan. tsasada@kcch.jp.
Abstract
INTRODUCTION: TCR and BCR repertoire diversity plays a critical role in tumor immunity. Thus, analysis of TCR and BCR repertoires might help predict the clinical efficacy of anti-PD-1 treatment. METHODS: Blood samples from 30 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibody were collected before and six weeks after treatment initiation. The clinical significance of TCR and BCR repertoire diversity in peripheral blood was evaluated in all the enrolled patients (n = 30) or in the subset with (n = 10) or without (n = 20) EGFR/ALK mutation. RESULTS: TCR and BCR diversity was significantly correlated at baseline (R = 0.65; P = 1.6 × 10-4) and on treatment (R = 0.72; P = 1.2 × 10-5). Compared to non-responders (SD or PD), responders (PR) showed significantly decreased TCR and BCR diversity after treatment in the EGFR/ALK wild-type subset (P = 0.0014 and P = 0.034, respectively), but not in all the enrolled patients. The post-treatment reduction in TCR and BCR repertoire diversity was also significantly associated with the occurrence of adverse events in the EGFR/ALK wild-type subset (P = 0.022 and P = 0.014, respectively). Patients with more reduced TCR diversity showed better progression-free survival (PFS) in the EGFR/ALK wild-type subset (P = 0.011) but not in the mutant subset. CONCLUSIONS: These findings suggest the clinical significance of changes in peripheral TCR and BCR repertoire diversity after anti-PD-1 treatment in patients with NSCLC without EGFR/ALK mutation. Monitoring of the peripheral TCR and BCR repertoires may serve as a surrogate marker for the early detection of EGFR/ALK wild-type NSCLC patients who would benefit from anti-PD-1 treatment.
INTRODUCTION: TCR and BCR repertoire diversity plays a critical role in tumor immunity. Thus, analysis of TCR and BCR repertoires might help predict the clinical efficacy of anti-PD-1 treatment. METHODS: Blood samples from 30 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibody were collected before and six weeks after treatment initiation. The clinical significance of TCR and BCR repertoire diversity in peripheral blood was evaluated in all the enrolled patients (n = 30) or in the subset with (n = 10) or without (n = 20) EGFR/ALK mutation. RESULTS: TCR and BCR diversity was significantly correlated at baseline (R = 0.65; P = 1.6 × 10-4) and on treatment (R = 0.72; P = 1.2 × 10-5). Compared to non-responders (SD or PD), responders (PR) showed significantly decreased TCR and BCR diversity after treatment in the EGFR/ALK wild-type subset (P = 0.0014 and P = 0.034, respectively), but not in all the enrolled patients. The post-treatment reduction in TCR and BCR repertoire diversity was also significantly associated with the occurrence of adverse events in the EGFR/ALK wild-type subset (P = 0.022 and P = 0.014, respectively). Patients with more reduced TCR diversity showed better progression-free survival (PFS) in the EGFR/ALK wild-type subset (P = 0.011) but not in the mutant subset. CONCLUSIONS: These findings suggest the clinical significance of changes in peripheral TCR and BCR repertoire diversity after anti-PD-1 treatment in patients with NSCLC without EGFR/ALK mutation. Monitoring of the peripheral TCR and BCR repertoires may serve as a surrogate marker for the early detection of EGFR/ALK wild-type NSCLCpatients who would benefit from anti-PD-1 treatment.
Entities:
Keywords:
Anti-PD-1 antibody; B cell receptor (BCR) repertoire; EGFR/ALK; Non-small cell lung cancer (NSCLC); T cell receptor (TCR) repertoire
Authors: Toni K Choueiri; Laurence Albiges; Michael B Atkins; Ziad Bakouny; Gennady Bratslavsky; David A Braun; Naomi B Haas; John B A G Haanen; A Ari Hakimi; Michael A S Jewett; Eric Jonasch; William G Kaelin; Payal Kapur; Chris Labaki; Bryan Lewis; David F McDermott; Sumanta K Pal; Kevin Pels; Susan Poteat; Thomas Powles; W Kimryn Rathmell; Brian I Rini; Sabina Signoretti; Nizar M Tannir; Robert G Uzzo; Hans J Hammers Journal: Clin Cancer Res Date: 2022-03-01 Impact factor: 13.801