Immune-Checkpoint Blockade Opposes CD8⁺ T-cell Suppression in Human and Murine Cancer.

ABSTRACT: Immune-checkpoint blockade enhances antitumor responses against cancers. One cancer type that is sensitive to checkpoint blockade is squamous cell carcinoma of the head and neck (SCCHN), which we use here to study limitations of this treatment modality. We observed that CD8⁺ tumor-infiltrating lymphocytes (TILs) in SCCHN and melanoma express excess immune checkpoints components PD-1 and Tim-3 and are also CD27^-/CD28^-, a phenotype we previously associated with immune dysfunction and suppression. In ex vivo experiments, patients' CD8⁺ TILs with this phenotype suppressed proliferation of autologous peripheral blood T cells. Similar phenotype and function of TILs was observed in the TC-1 mouse tumor model. Treatment of TC-1 tumors with anti-PD

SUBMITTER: Pfannenstiel LW 

PROVIDER: S-EPMC6476322 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature