Abstract LB009: Dynamic changes in the compositions of cancer associated-fibroblasts correlate with clinical outcome in breast cancer

Abstract:: Cancer associated fibroblasts (CAFs) are prevalent in carcinomas. CAFs are also heterogeneous and perform various tumor-promoting tasks. Understanding whether distinct CAF-subsets exert specific functions, and how the composition of CAFs changes as tumors evolve could improve the accuracy of cancer treatment. Here, we analyzed thousands of CAFs by single-cell RNA-sequencing and index-sorting at several timepoints along breast tumor progression in mice, revealing distinct CAF-subsets. We discovered that the transcriptional programs of these subsets change over time, shifting from an immune-regulatory program at earlier timepoints to wound-healing and antigen-presenting programs at later timepoints, indicating that the composition and functions of CAFs are dynamic. We also found the two main CAF subsets in human breast tumors, wherein their ratio was associated with disease outcome. This association was particularly correlated with BRCA mutations in triple-negative breast cancer. Our findings indicate that the diverse composition of CAFs in breast cancer changes over time as tumors progress, and that these changes are linked to disease outcome.

Authors:: G Friedman, O Levi-Galibov, E David, C Bornstein, A Giladi, M Dadiani, A Mayo, C Halperin, M Pevsner-Fischer, H Lavon, S Mayer, R Nevo, Y Stein, N Balint-Lahat, I Barshack, HR Ali, C Caldas, EN Gal-Yam, U Alon, I Amit, R Scherz-Shouval

Themes