An innate-like V?1+ ?? T cell compartment in the human breast is associated with remission in triple-negative breast cancer.

ABSTRACT: Innate-like tissue-resident ?? T cell compartments capable of protecting against carcinogenesis are well established in mice. Conversely, the degree to which they exist in humans, their potential properties, and their contributions to host benefit are mostly unresolved. Here, we demonstrate that healthy human breast harbors a distinct ?? T cell compartment, primarily expressing T cell receptor (TCR) V?1 chains, by comparison to V?2 chains that predominate in peripheral blood. Breast-resident V?1+ cells were functionally skewed toward cytolysis and IFN-? production, but not IL-17, which has been linked with inflammatory pathologies. Breast-resident V?1+ cells could be activated innately via the NKG2D receptor, whereas neighboring CD8+ ?? T cells required TCR signaling. A comparable population of V?1+ cells was found in human breast tumors, and when paired tumor and nonmalignant samples from 11 patients with triple-negative breast cancer were analyzed, progression-free and overall survival correlated with V?1+ cell representation, but not with either total ?? T cells or V?2+ T cells. As expected, progression-free survival also correlated with ?? TCRs. However, whereas in most cases TCR?? repertoires focused, typical of antigen-specific responses, this was not observed for V?1+ cells, consistent with their innate-like responsiveness. Thus, maximal patient benefit may accrue from the collaboration of innate-like responses mounted by tissue-resident V?1+ compartments and adaptive responses mounted by ?? T cells.

SUBMITTER: Wu Y 

PROVIDER: S-EPMC6877350 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature