H Arias-Pulido1, A Cimino-Mathews2,3, N Chaher4, C Qualls5, N Joste5, C Colpaert6, J D Marotti7, M Foisey8, E R Prossnitz5, L A Emens3, S Fiering8. 1. Departments of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 621 Rubin Building - HB7936; 1 Medical Center Drive, Lebanon, NH, 03756, USA. hugo.ariaspulido@dartmouth.edu. 2. Departments of Pathology, The Johns Hopkins University School of Medicine and Bloomberg-Kimmel Institute for Immunotherapy, Baltimore, MD, USA. 3. Departments of Oncology, The Johns Hopkins University School of Medicine and Bloomberg-Kimmel Institute for Immunotherapy, Baltimore, MD, USA. 4. Department of Pathology, Centre Pierre et Marie Curie et Faculté de Médecine d'Alger, Algiers, Algeria. 5. Departments of Pathology, Mathematics and Statistics, and Internal Medicine, The University of New Mexico Comprehensive Cancer Center, and Health Sciences Center, Albuquerque, NM, USA. 6. Department of Pathology, Oncology Centre, GZA Hospitals, Iridium Cancer Net, Antwerp, Belgium. 7. Pathology and Laboratory Medicine, and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. 8. Departments of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 621 Rubin Building - HB7936; 1 Medical Center Drive, Lebanon, NH, 03756, USA.
Abstract
PURPOSE: The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples. METHODS: PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1+ tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1+ TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. RESULTS: PD-L1+ tumor cells, PD-L1+ TILs, and CD20+ TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1+ tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20+ TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1+ TILs strongly correlated with high TILs, CD20+ TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20+ TILs and PD-L1+ TILs (CD20+TILs/PD-L1+TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20+ TILs or PD-L1+ TILs alone. In multivariate analyses, CD20+TILs/PD-L1+TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37-0.77) and TN IBC (HR: 0.39 95% CI 0.17-0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43-0.85) and TN IBC (HR: 0.38 95% CI 0.17-0.83). CONCLUSION: CD20+TILs/PD-L1+TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.
PURPOSE: The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples. METHODS:PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1+ tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1+ TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. RESULTS:PD-L1+ tumor cells, PD-L1+ TILs, and CD20+ TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1+ tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20+ TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1+ TILs strongly correlated with high TILs, CD20+ TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20+ TILs and PD-L1+ TILs (CD20+TILs/PD-L1+TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20+ TILs or PD-L1+ TILs alone. In multivariate analyses, CD20+TILs/PD-L1+TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37-0.77) and TN IBC (HR: 0.39 95% CI 0.17-0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43-0.85) and TN IBC (HR: 0.38 95% CI 0.17-0.83). CONCLUSION:CD20+TILs/PD-L1+TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.
Entities:
Keywords:
CD20; Immuno-oncology; Inflammatory breast cancer; PD-L1; Patient outcome; Triple-negative
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