Format

Send to

Choose Destination
Sci Transl Med. 2019 Oct 9;11(513). pii: eaax9364. doi: 10.1126/scitranslmed.aax9364.

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

Author information

1
Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London SE1 9RT, UK.
2
Immunosurveillance Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
3
Breast Cancer Now Research Unit, Innovation Hub, Cancer Centre at Guy's Hospital, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK.
4
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London WC1E 6DD, UK.
5
St John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
6
KHP Cancer Biobank, Innovation Hub, Cancer Centre at Guy's Hospital, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK.
7
Bill Lyons Informatics Centre, University College London Cancer Institute, University College London, London WC1E 6DD, UK.
8
Breast Cancer Now Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
9
Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London SE1 9RT, UK. adrian.hayday@kcl.ac.uk.

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.

PMID:
31597756
PMCID:
PMC6877350
[Available on 2020-04-09]
DOI:
10.1126/scitranslmed.aax9364

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center