Breast cancer is marked by specific, Public T-cell receptor CDR3 regions shared by mice and humans

Miri Gordin, Hagit Philip, Alona Zilberberg, Moriah Gidoni, Raanan Margalit, Christopher Clouser, Kristofor Adams, Francois Vigneault, Irun R. Cohen, Gur Yaari, Sol Efroni

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The partial success of tumor immunotherapy induced by checkpoint blockade, which is not antigen-specific, suggests that the immune system of some patients contain antigen receptors able to specifically identify tumor cells. Here we focused on T-cell receptor (TCR) repertoires associated with spontaneous breast cancer. We studied the alpha and beta chain CDR3 domains of TCR repertoires of CD4 T cells using deep sequencing of cell populations in mice and applied the results to published TCR sequence data obtained from human patients. We screened peripheral blood T cells obtained monthly from individual mice spontaneously developing breast tumors by 5 months. We then looked at identical TCR sequences in published human studies; we used TCGA data from tumors and healthy tissues of 1,256 breast cancer resections and from 4 focused studies including sequences from tumors, lymph nodes, blood and healthy tissues, and from single cell dataset of 3 breast cancer subjects. We now report that mice spontaneously developing breast cancer manifest shared, Public CDR3 regions in both their alpha and beta and that a significant number of women with early breast cancer manifest identical CDR3 sequences. These findings suggest that the development of breast cancer is associated, across species, with bio-marker, exclusive TCR repertoires.

Original languageEnglish
Article numbere1008486
JournalPLoS Computational Biology
Volume17
Issue number1
DOIs
StatePublished - 19 Jan 2021

Bibliographical note

Publisher Copyright:
Copyright: © 2021 Gordin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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