Faculty, Staff and Student Publications

Publication Date

10-11-2022

Journal

Nature Communications

Abstract

Analyzing antigen-specific T cell responses at scale has been challenging. Here, we analyze three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls. Although melanoma-associated antigen (MAA) -specific TCRs are restricted to individuals, they share sequence similarities that allow us to build classifiers for predicting anti-MAA T cells. The frequency of anti-MAA T cells distinguishes melanoma patients from healthy and predicts metastatic recurrence from primary melanoma. Anti-MAA T cells have stem-like properties and frequent interactions with regulatory T cells and tumor cells via Galectin9-TIM3 and PVR-TIGIT -axes, respectively. In the responding patients, the number of expanded anti-MAA clones are higher after the anti-PD1(+anti-CTLA4) therapy and the exhaustion phenotype is rescued. Our systems immunology approach paves the way for understanding antigen-specific responses in human disorders.

Keywords

Hepatitis A Virus Cellular Receptor 2, Humans, Melanoma, RNA, Receptors, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta

DOI

10.1038/s41467-022-33720-z

PMID

36220826

PMCID

PMC9553985

PubMedCentral® Posted Date

10-11-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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