Back to Search Start Over

T-cell receptor determinants of response to chemoradiation in locally-advanced HPV16-driven malignancies.

Authors :
Nenclares, Pablo
Larkeryd, Adrian
Manodoro, Floriana
Lee, Jen Y.
Lalondrelle, Susan
Gilbert, Duncan C.
Punta, Marco
O'Leary, Ben
Rullan, Antonio
Sadanandam, Anguraj
Chain, Benny
Melcher, Alan
Harrington, Kevin J.
Bhide, Shreerang A.
Source :
Frontiers in Oncology; 2024, p1-15, 15p
Publication Year :
2024

Abstract

Background: The effect of chemoradiation on the anti-cancer immune response is being increasingly acknowledged; however, its clinical implications in treatment responses are yet to be fully understood. Human papillomavirus (HPV)-driven malignancies express viral oncogenic proteins which may serve as tumor-specific antigens and represent ideal candidates for monitoring the peripheral T-cell receptor (TCR) changes secondary to chemoradiotherapy (CRT). Methods: We performed intra-tumoral and pre- and post-treatment peripheral TCR sequencing in a cohort of patients with locally-advanced HPV16-positive cancers treated with CRT. An in silico computational pipeline was used to cluster TCR repertoire based on epitope-specificity and to predict affinity between these clusters and HPV16-derived epitopes. Results: Intra-tumoral repertoire diversity, intra-tumoral and post-treatment peripheral CDR3b similarity clustering were predictive of response. In responders, CRT triggered an increase peripheral TCR clonality and clonal relatedness. Post-treatment expansion of baseline peripheral dominant TCRs was associated with response. Responders showed more baseline clustered structures of TCRs maintained post-treatment and displayed significantly more maintained clustered structures. When applying clustering by TCR-specificity methods, responders displayed a higher proportion of intra-tumoral TCRs predicted to recognise HPV16 peptides. Conclusions: Baseline TCR characteristics and changes in the peripheral T-cell clones triggered by CRT are associated with treatment outcome. Maintenance and boosting of pre-existing clonotypes are key elements of an effective anticancer immune response driven by CRT, supporting a paradigm in which the immune system plays a central role in the success of CRT in current standard-ofcare protocols. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
2234943X
Database :
Complementary Index
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
174904886
Full Text :
https://doi.org/10.3389/fonc.2023.1296948