PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8⁺ T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination.

ABSTRACT: The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8⁺ T cell (T_CD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse T_CD8 exhaustion/anergy. However, whether they alter the epitope breadth of T_CD8 responses remains unclear. This is an important question because subdominant T_CD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity. We have addressed this question in an in vivo model of T_CD8 responses to well-defined epitopes of a clinically relevant oncoprotein, large T Ag. We found that unlike othe

SUBMITTER: Memarnejadian A 

PROVIDER: S-EPMC5731479 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature