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. 2017 May 30;8(31):51641-51651.
doi: 10.18632/oncotarget.18305. eCollection 2017 Aug 1.

PD-L1 and intratumoral immune response in breast cancer

Zhi-Qiang Wang  1   2 , Katy Milne  1 , Heather Derocher  1   3 , John R Webb  1   3 , Brad H Nelson  1   3   4 , Peter H Watson  1   2
Affiliations

PD-L1 and intratumoral immune response in breast cancer

Zhi-Qiang Wang et al. Oncotarget. .

Abstract

Purpose: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance.

Methods: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype.

Results: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16.5%) cases and associated with known indicators of poor prognosis, including low patient age, high tumor grade, ER/PR negative status, but not with outcome. However, in the Triple Negative breast cancer subset PD-L1 was associated with better recurrence free survival (RFS) especially within the Basal-like subset (Hazard ratio = 0.39, 95% CI = 0.22 - 0.86, p = 0.018). Combined PD-L1/epithelial CD8 positive status was also strongly associated with better RFS and OS (Hazard ratio = 0.12, 95% CI = 0.10 - 0.71, p = 0.010 and Hazard ratio = 0.11, 95% CI = 0.11 - 0.68, p = 0.006 respectively) in the Basal-like subgroup.

Conclusions: PD-L1 expression is associated with better patient survival in Basal-like breast cancer.

Keywords: CD4; CD68; CD8; PD-L1; breast cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Immunohistochemical staining showing PD-L1 positive staining in tumor cells (A) and TIL (B). Magnification ×400. Bar 200 um.
Figure 2
Figure 2. Prognostic impact of PD-L1 and CD8 in breast cancer
Kaplan–Meier plots showing recurrence free survival (RFS) in entire cohort, TNNB and Basal-like subgroups stratified according to the expression status of intra-epithelial PD-L1 (A, D, G) and eCD8 (B, E, H) and PD-L1/eCD8 in combination (C, F, I). The log-rank test was used to compare curves, and p-values less than 0.05 were considered significant. NS = no significance.
Figure 3
Figure 3
Associations between tumor cell PD-L1 expression and TIL cell densities within Non-TNBC (A), TNBC (B), TNNB (C) and Basal-like subtypes (D). Bars represent means +/- standard error. Black and grey bars represent intra-epithelial and intra-stromal densities of CD8, CD4, and CD68 positive TIL respectively. Non-TNBC = Luminal A + Luminal B + Her2; TNBC cases = TNNB (Triple Negative Non Basal) + Basal-like subtypes; NS = no significance, *p ≤ 0.05, ** p ≤ 0.01, ***p ≤ 0.001.
See this image and copyright information in PMC

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