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

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

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Author contributions

Qian Zhu drafted the manuscript. Mu-Yan Cai and Chang-Long Chen collected the tissue specimens and patient information. Hao Hu conducted the IHC analysis. De-Sheng Weng, Jing-Jing Zhao and Huan-Xin Lin performed the statistical analyses. Mu-Yan Cai and Min Li conducted the IHC analysis. Ling Guo participated in designing the study and editing the manuscript. JianChuan Xia conceived the study and guided the entire project. All authors read and approved the final manuscript.