Research ArticleCancer

An innate-like Vδ1+ γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer

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Science Translational Medicine  09 Oct 2019:
Vol. 11, Issue 513, eaax9364
DOI: 10.1126/scitranslmed.aax9364

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γδ T cells: Guarding and defending tissues

Specific γδ T cell subsets are known to populate tissues such as the skin and gut. To ascertain γδ T cell participation in breast cancer surveillance, Wu et al. isolated cells from grid cultures of human breast tissue. They observed cytolytic innate-like Vδ1+ T cells in healthy human breast tissue as well as tumor tissue. Analysis of a small cohort of women with triple-negative breast cancer revealed that these Vδ1+ T cells were associated with remission and overall survival. These results demonstrate that human tissue-resident γδ T cells may affect breast cancer progression; these cells could be key to existing or future immunotherapy interventions.

Abstract

Innate-like tissue-resident γδ 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 γδ T cell compartment, primarily expressing T cell receptor (TCR) Vδ1 chains, by comparison to Vδ2 chains that predominate in peripheral blood. Breast-resident Vδ1+ cells were functionally skewed toward cytolysis and IFN-γ production, but not IL-17, which has been linked with inflammatory pathologies. Breast-resident Vδ1+ cells could be activated innately via the NKG2D receptor, whereas neighboring CD8+ αβ T cells required TCR signaling. A comparable population of Vδ1+ 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 Vδ1+ cell representation, but not with either total γδ T cells or Vδ2+ T cells. As expected, progression-free survival also correlated with αβ TCRs. However, whereas in most cases TCRαβ repertoires focused, typical of antigen-specific responses, this was not observed for Vδ1+ cells, consistent with their innate-like responsiveness. Thus, maximal patient benefit may accrue from the collaboration of innate-like responses mounted by tissue-resident Vδ1+ compartments and adaptive responses mounted by αβ T cells.

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