Tumor Immune Microenvironment Changes by Multiplex Immunofluorescence Staining in a Pilot Study of Neoadjuvant Talazoparib for Early-Stage Breast Cancer Patients with a Hereditary BRCA Mutation
Tapsi Kumar, Evie Hobbs, Fei Yang, Jeffrey T Chang, Alejandro Contreras, Edwin Roger Parra Cuentas, Haven Garber, Sanghoon Lee, Yiling Lu, Marion E Scoggins, Beatriz E Adrada, Gary J Whitman, Banu K Arun, Elizabeth A Mittendorf, Jennifer K Litton, Tapsi Kumar, Evie Hobbs, Fei Yang, Jeffrey T Chang, Alejandro Contreras, Edwin Roger Parra Cuentas, Haven Garber, Sanghoon Lee, Yiling Lu, Marion E Scoggins, Beatriz E Adrada, Gary J Whitman, Banu K Arun, Elizabeth A Mittendorf, Jennifer K Litton
Abstract
Purpose: The immunological profile of early-stage breast cancer treated with neoadjuvant PARP inhibitors has not been described. The aim of this study was to delineate the changes in the tumor immune microenvironment (TiME) induced by talazoparib.
Patients and methods: Patients with operable germline BRCA1/2 pathogenic variant (gBRCA1/2+) breast cancer were enrolled in a feasibility study of neoadjuvant talazoparib. Thirteen patients who received 8 weeks of neoadjuvant talazoparib were available for analysis, including 11 paired pre- and post-talazoparib core biopsies. Treatment-related changes in tumor-infiltrating lymphocytes were examined and immune cell phenotypes and their spatial distribution in the TiME were identified and quantified by multiplex immunofluorescence using a panel of 6 biomarkers (CD3, CD8, CD68, PD-1, PD-L1, and CK).
Results: Neoadjuvant talazoparib significantly increased infiltrating intratumoral and stromal T-cell and cytotoxic T-cell density. There was no difference in PD-1 or PD-L1 immune cell phenotypes in the pre- and post-talazoparib specimens and PD-L1 expression in tumor cells was rare in this cohort. Spatial analysis demonstrated that pre-talazoparib interactions between macrophages and T cells may correlate with pathologic complete response.
Conclusions: This is the first study with phenotyping to characterize the immune response to neoadjuvant talazoparib in patients with gBRCA1/2+ breast cancer. These findings support an emerging role for PARP inhibitors in enhancing tumor immunogenicity. Further investigation of combinatorial strategies is warranted with agents that exploit the immunomodulatory effects of PARP inhibitors on the TiME.
Trial registration: ClinicalTrials.gov NCT02282345.
Conflict of interest statement
Conflicts of interest:
E. A. Mittendorf reports personal financial interests: sponsored research agreement from Glaxo SmithKline; honoraria from Physician Education Resource; compensated service on Scientific Advisory Boards for Exact Sciences (formerly Genomic Health), Merck, and Roche/Genentech; and uncompensated service on Steering Committees for BMS, Lilly, Roche/Genentech. E. A. Mittendorf reports institutional financial interests: Clinical trial funding from Roche/Genentech (via SU2C grant). G. J. Whitman is a shareholder of Pfizer and editor for UpToDate. JLitton reports personal financial interests: sponsored research agreements from Pfizer/Medivation, Genentech, BMS, Novartis, GSK, Zenith, Merck, EMD-Serono and Astra-Zenica. And has had uncompensated service on advisory Boards and Steering Committees for Pfizer, Astra-Zeneca and Ayala Pharmaceuticals. The other authors declare no potential conflicts of interest.
©2022 American Association for Cancer Research.
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Source: PubMed