Breast Cancer Research and Treatment
The combined presence of CD20 + B cells and PD-L1 + tumor-
inﬁltrating lymphocytes in inﬂammatory breast cancer is prognostic
of improved patient outcome
· A. Cimino‑Mathews
· N. Chaher
· C. Qualls
· N. Joste
· C. Colpaert
· J. D. Marotti
· E. R. Prossnitz
· L. A. Emens
· S. Fiering
Received: 17 March 2018 / Accepted: 19 May 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
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
was scored in tumor-inﬁltrating B cells. Kaplan–Meier curves and Cox proportional hazard models were used for survival
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
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) 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,
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).
TILs status represents an independent favorable prognostic factor in IBC and TN IBC, sug-
gesting 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 PD-L1 · CD20 · Immuno-oncology · Inﬂammatory breast cancer · Triple-negative · Patient outcome
IBC Inﬂammatory breast cancer.
PD-1 Programmed cell death 1.
PD-L1 Programmed cell death ligand 1.
TILs Tumor-inﬁltrating lymphocytes.
pCR Pathological complete response.
BCSS Breast cancer-speciﬁc survival.
DFS Disease-free survival.
HR Hazard ratio.
CI Conﬁdential interval.
NACT Neoadjuvant chemotherapy.
FFPETs Formalin-ﬁxed paraﬃn embedded tissues.
Inﬂammatory breast cancer (IBC) is a rare, poorly under-
stood, and highly aggressive form of breast cancer. It
accounts for less than 3% of all breast cancers, but is
H. Arias-Pulido and A. Cimino-Mathews have contributed equally
to this study.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s1054 9-018-4834-7) contains
supplementary material, which is available to authorized users.
* H. Arias-Pulido
Extended author information available on the last page of the article