Peripheral CD8⁺ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma.

ABSTRACT: Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable therapeutic benefit. To explore this in peripheral samples, we characterized CD8⁺ T cell gene expression across a cohort of patients with MM receiving anti-PD-1 alone (sICB) or in combination with anti-CTLA-4 (cICB). Whereas CD8⁺ transcriptional responses to sICB and cICB involve a shared gene set, the magnitude of cICB response is over fourfold greater, with preferential induction of mitosis- and interferon-related genes. Early samples from patients with durable clinical benefit demonstrated overexpression of T cell receptor-encoding genes. By mapping T cell receptor clonality, we find that responding patients have more large clones (those occupying >0.5% of repertoire)

SUBMITTER: Fairfax BP 

PROVIDER: S-EPMC7611047 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature