The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

H. Arias-Pulido, Ashley M Cimino-Mathews, N. Chaher, C. Qualls, N. Joste, C. Colpaert, J. D. Marotti, M. Foisey, E. R. Prossnitz, L. A. Emens, S. Fiering

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Jun 1 2018

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Inflammatory Breast Neoplasms
Tumor-Infiltrating Lymphocytes
B-Lymphocytes
Triple Negative Breast Neoplasms
Stromal Cells
Neoplasms
Disease-Free Survival
Survival Analysis
Proportional Hazards Models

Keywords

  • CD20
  • Immuno-oncology
  • Inflammatory breast cancer
  • Patient outcome
  • PD-L1
  • Triple-negative

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. / Arias-Pulido, H.; Cimino-Mathews, Ashley M; Chaher, N.; Qualls, C.; Joste, N.; Colpaert, C.; Marotti, J. D.; Foisey, M.; Prossnitz, E. R.; Emens, L. A.; Fiering, S.

In: Breast Cancer Research and Treatment, 01.06.2018, p. 1-10.

Research output: Contribution to journalArticle

Arias-Pulido, H. ; Cimino-Mathews, Ashley M ; Chaher, N. ; Qualls, C. ; Joste, N. ; Colpaert, C. ; Marotti, J. D. ; Foisey, M. ; Prossnitz, E. R. ; Emens, L. A. ; Fiering, S. / The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. In: Breast Cancer Research and Treatment. 2018 ; pp. 1-10.
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title = "The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome",
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.",
keywords = "CD20, Immuno-oncology, Inflammatory breast cancer, Patient outcome, PD-L1, Triple-negative",
author = "H. Arias-Pulido and Cimino-Mathews, {Ashley M} and N. Chaher and C. Qualls and N. Joste and C. Colpaert and Marotti, {J. D.} and M. Foisey and Prossnitz, {E. R.} and Emens, {L. A.} and S. Fiering",
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T1 - The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

AU - Arias-Pulido, H.

AU - Cimino-Mathews, Ashley M

AU - Chaher, N.

AU - Qualls, C.

AU - Joste, N.

AU - Colpaert, C.

AU - Marotti, J. D.

AU - Foisey, M.

AU - Prossnitz, E. R.

AU - Emens, L. A.

AU - Fiering, S.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - CD20

KW - Immuno-oncology

KW - Inflammatory breast cancer

KW - Patient outcome

KW - PD-L1

KW - Triple-negative

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U2 - 10.1007/s10549-018-4834-7

DO - 10.1007/s10549-018-4834-7

M3 - Article

C2 - 29858752

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JO - Breast Cancer Research and Treatment

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