Journal article

RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors

Sherene Loi, Sathana Dushyanthen, Paul A Beavis, Roberto Salgado, Carsten Denkert, Peter Savas, Susan Combs, David L Rimm, Jennifer M Giltnane, Monica V Estrada, Violeta Sanchez, Melinda E Sanders, Rebecca S Cook, Mark A Pilkinton, Simon A Mallal, Kai Wang, Vincent A Miller, Phil J Stephens, Roman Yelensky, Franco D Doimi Show all

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2016

Abstract

PURPOSE: Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking. EXPERIMENTAL DESIGN: We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer. RESULTS: Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras-MAPK signaling were..

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Grants

Awarded by Susan G. Komen for the Cure Foundation


Awarded by NIH/NCI


Awarded by Breast Cancer Specialized Program of Research Excellence (SPORE)


Awarded by Vanderbilt-Ingram Cancer Center Support Grant


Awarded by National Breast Cancer Foundation


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

J.M. Balko was supported by the Inflammatory Breast Cancer (IBC) Network Foundation, Susan G. Komen for the Cure Foundation CCR14299052, the NIH/NCI (1K99CA181491), the Breast Cancer Specialized Program of Research Excellence (SPORE) P50 CA098131, Vanderbilt-Ingram Cancer Center Support Grant P30 CA68485. C.L. Arteaga is also supported by Susan G. Komen for the Cure Foundation grant SAC100013. S. Loi, S. Dushyanthen, P.A. Beavis, P. Savas, and P.K. Darcy are supported by the National Breast Cancer Foundation of Australia. S. Loi is also supported by Cancer Council Victoria, Australia.