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. 2017 Apr 27;6(5):e1312240.
doi: 10.1080/2162402X.2017.1312240. eCollection 2017.

Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

Qian Zhu  1   2 , Mu-Yan Cai  1   3 , Chang-Long Chen  1   2 , Hao Hu  4 , Huan-Xin Lin  1   5 , Min Li  1   3 , De-Sheng Weng  1   2 , Jing-Jing Zhao  1   2 , Ling Guo  1   6 , Jian-Chuan Xia  1   2
Affiliations

Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

Qian Zhu et al. Oncoimmunology. .

Abstract

Programmed death ligand 1 (PD-L1) expression represents a mechanism of immune escape by inhibiting T cell immunity. This study systematically evaluated the expression of PD-L1, spatial distribution of CD3+ immune cells and the relationship of both factors to survival in nasopharyngeal carcinoma (NPC) patients. A total of 209 NPC patients treated between 1991 and 2000 were included. Pairs of TMAs were immunohistochemically stained with PD-L1 and CD3. Survival analysis was evaluated according to PD-L1 status and the spatial distribution of CD3+ immune cells in the primary lesion microenvironment. PD-L1 staining was observed on tumor cells and tumor-infiltrating immune cells (TILs); however, PD-L1-positive immune cells were more common (98/209) than PD-L1-positive tumor cells (68/209). Limited numbers of intra-tumoral CD3+ T cells (median number: 20) were detected. Patients with higher CD3+ T cell infiltration, both intratumorally and peritumorally, had higher PD-L1 expression on tumor cells (both p < 0.001) and immune cells (p = 0.002 and p < 0.001, respectively). Increasing intratumoral CD3 infiltration was correlated with increased overall survival (OS) (p = 0.008) and disease-free survival (DFS) (p = 0.003). Nevertheless, patients with low levels of peritumoral TILs showed superior OS (p = 0.557) and DFS to those with higher levels of peritumoral TILs (p = 0.671). Moreover, type classification based on intratumoral CD3 infiltration and tumor cell PD-L1 expression was an independent prognostic factor for NPC patients. PD-L1 expression on tumor cells is a favorable prognosis factor in NPC patients with pre-existing intratumor-infiltrating lymphocytes.

Keywords: Nasopharyngeal carcinoma; PD-L1; prognosis; tumor-infiltrating lymphocytes.

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Figures

Figure 1.
Figure 1.
Evaluation of CD3, PD-L1 protein and their associations in nasopharyngeal carcinoma patients. Tumor and immune cell PD-L1 protein (A) and intratumoral and peritumoral CD3+ lymphocytes (B). Correlation between intratumoral (C) or peritumoral CD3+ lymphocytes and TCs-PD-L1 (D), and correlation between intratumoral (E) or peritumoral CD3+ lymphocytes (F) and ICs- PD-L1 expression.
Figure 2.
Figure 2.
Survival curves of different distributions of CD3+ TILs. Kaplan–Meier plots of OS (A) and DFS (B) according to the percentage of TILs. OS (C and E) and DFS (D and F) based on intratumoral and peritumoral CD3+ lymphocytes.
Figure 3.
Figure 3.
Survival curves of different distributions of PD-L1+ cells. The present study analyzed OS (A and C) and DFS (B and D) based on TCs-PD-L1 and ICs-PD-L1.
Figure 4.
Figure 4.
Comparison of survival according to staging system in 209 NPC patients. OS and DFS analyses according to the stage classification based on CD3+ lymphocytes and TCs-PD-L1 (A and B). Survival analysis based on intratumoral CD3+ lymphocytes and TCs-PD-L1 (C and D).
See this image and copyright information in PMC

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