T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma.

BACKGROUND

T cell receptor (TCR) signaling profile is a fundamental property that underpins both adaptive and innate immunity in the host. Despite its potential clinical relevance, the TCR repertoire in peripheral blood has not been thoroughly explored for its value as an immunotherapy efficacy biomarker in head and neck squamous cell carcinoma (HNSCC). The purpose of the present study is to characterize and compare the TCR repertoire in peripheral blood mononuclear cells (PBMC) from patients with HNSCC treated with the combination of cetuximab and nivolumab.

METHODS

We used the immunoSEQ assay to sequence the TCR beta (TCR-B) chain repertoire from serially obtained PBMC at baseline and during the treatments from a total of 41 patients who received the combination (NCT03370276). Key TCR repertoire metrics, including diversity and clonality, were calculated and compared between patients with different therapy responses and clinical characteristics (eg, human papillomavirus (HPV) status and smoking history). Patient survival outcomes were compared according to patient groups stratified by the TCR-B clonotyping. To confirm the observed patterns in TCR spectrum, samples from patients who achieved complete response (CR) and partial response (PR) were further profiled with the immunoSEQ deep resolution assay.

RESULTS

Our data indicated that the patients who achieved CR and PR had an increased TCR sequence diversity in their baseline samples, this tendency being more pronounced in HPV-negative patients or those with a smoking history. Notably, the CR/PR group had the lowest proportion of patients with oligoclonal TCR clones (2 out of 8 patients), followed by the stable disease group (9 out of 20 patients) and lastly the progressive disease group (7 out of 10 patients). An overall trend toward favorable patient survival was also observed in the polyclonal group. Finally, we reported the shared TCR clones across patients within the same response group, as well as the shared clones by aligning immunoSEQ reads with TCR data retrieved from The Cancer Genome Atlas- head and neck squamous cell carcinoma (TCGA-HNSC) cohort.

CONCLUSIONS

Our data suggest that, despite the great clinical heterogeneity of HNSCC and the limited responders in the present cohort, the peripheral TCR repertoires from pretreatment PBMC may be developed as biomarkers for the benefit of immunotherapy in HNSCC.

Informations de copyright

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: CHC—honoraria from Bristol Myers Squibb, CUE, Sanofi, Mirati, Merck, and Exelixis for ad hoc Scientific Advisory Board participation. CS—honoraria from Armo, Bergen Bio, AbbVie, and Lilly Oncology for ad hoc Scientific Advisory Board participation. NS—honoraria from Pfizer, Merck, Aduro, Rakuten, CUE, and Blupoint, Eisai, AstraZeneca, WebMD, Mirati, Reach MD, Vaccinex, Kura, Biontech, GSK, Aduro, Pfizer for ad hoc Scientific Advisory Board or Data Safety Monitoring Committee and research funding Bristol Myers Squibb and Exelixis. JRCG—Honorarium from Alloy Therapeutics and Anixa Biosciences; stock options in Alloy Therapeutics, Anixa Biosciences and Compass Therapeutics; intellectual property with Anixa Biosciences and Compass Therapeutics; sponsored research supported by Anixa Biosciences.The other authors do not have conflict of interest to declare.