Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 10, Pages 2881-2892Publisher
SPRINGER
DOI: 10.1007/s00262-021-02900-z
Keywords
T cell receptor (TCR) repertoire; B cell receptor (BCR) repertoire; Anti-PD-1 antibody; Non-small cell lung cancer (NSCLC); EGFR; ALK
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Funding
- AMED [JP20ae0101076]
- JSPS KAKENHI [JP18K19490]
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The diversity of TCR and BCR repertoires plays a critical role in tumor immunity, and analyzing them may help predict the clinical efficacy of anti-PD-1 treatment in NSCLC patients. Changes in peripheral TCR and BCR repertoire diversity after anti-PD-1 treatment could serve as a surrogate marker for early detection of EGFR/ALK wild-type NSCLC patients who would benefit from the 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 x 10(-4)) and on treatment (R = 0.72; P = 1.2 x 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.
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