Deng Rui, Lu Juan, Liu Xiong, Peng Xiao-Hong, Wang Jie, Li Xiang-Ping
Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Cancer Manag Res. 2020 Nov 12;12:11585-11596. doi: 10.2147/CMAR.S274913. eCollection 2020.
Tumour-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and provide a barrier against the cytotoxic effector functions of T cells and natural killer (NK) cells. Recently, TAMs have become increasingly recognised as an attractive target in combination therapy with PD-1/PD-L1 immuno-checkpoint blockades (ICBs). However, the relationship between PD-L1 expression and TAMs remains unknown in nasopharyngeal carcinoma (NPC).
A total of 212 NPC patients from Nanfang hospital were collected in this study. We evaluated the expression of PD-L1 in tumor cells, CD68 (pan-macrophages), and CD163 (M2-like macrophage) in NPC tissues using immunohistochemical (IHC) staining.
The positivity of PD-L1 on tumor cells was 61.3% (130/212). The infiltration densities of CD68+ cells and CD163+ cells in PD-L1-positive NPC tissues were significantly higher than those in PD-L1-negative NPC tissues (=0.0012 for CD68; <0.0001 for CD163). Logistic regression analysis showed that high densities of CD68+ macrophages and CD163+ TAMs were significantly associated with increased PD-L1 expression. Subgroup analyses demonstrated that a positive PD-L1 expression on tumor cells in combination with lower CD163+ TAMs density was significantly associated with favorable prognosis, whereas negative PD-L1 expression on tumor cells with higher CD163+ TAMs density was associated with worse prognosis.
The PD-L1 expression in tumor cells was positively correlated with TAMs density in tumor microenvironment of NPC, suggesting TAMs as a new target for combination therapy to improve the response rate of ICBs in NPC treatment.
肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中最丰富的免疫细胞，对T细胞和自然杀伤（NK）细胞的细胞毒性效应功能形成屏障。近来，TAMs作为联合PD-1/PD-L1免疫检查点阻断（ICB）疗法的一个有吸引力的靶点，越来越受到认可。然而，在鼻咽癌（NPC）中，PD-L1表达与TAMs之间的关系仍不清楚。
本研究收集了南方医院的212例NPC患者。我们采用免疫组织化学（IHC）染色评估NPC组织中肿瘤细胞、CD68（全巨噬细胞）和CD163（M2样巨噬细胞）中PD-L1的表达。
肿瘤细胞上PD-L1的阳性率为61.3%（130/212）。PD-L1阳性NPC组织中CD68+细胞和CD163+细胞的浸润密度显著高于PD-L1阴性NPC组织（CD68为P = 0.0012；CD163为P < 0.0001）。逻辑回归分析显示，CD68+巨噬细胞和CD163+ TAMs的高密度与PD-L1表达增加显著相关。亚组分析表明，肿瘤细胞上PD-L1阳性表达联合较低的CD163+ TAMs密度与良好预后显著相关，而肿瘤细胞上PD-L1阴性表达联合较高的CD163+ TAMs密度与较差预后相关。
NPC肿瘤微环境中肿瘤细胞的PD-L1表达与TAMs密度呈正相关，提示TAMs可作为联合治疗的新靶点，以提高ICB在NPC治疗中的反应率。
