Liu Shousheng, Kong Pengfei, Wang Xiaopai, Yang Lin, Jiang Chang, He Wenzhuo, Quan Qi, Huang Jinsheng, Xie Qiankun, Xia Xiaojun, Zhang Bei, Xia Liangping
State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Department of The VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Oncol Lett. 2019 Feb;17(2):2335-2343. doi: 10.3892/ol.2018.9826. Epub 2018 Dec 12.
The classification of tumor microenvironments according to the presence or absence of tumor infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) expression has been used to predict the efficacy of immune checkpoint inhibitor antibodies in several cancer types, not including colorectal cancer (CRC). The current study investigated the TIL/PD-L1 status of patients with CRC, particularly patients who presented as mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR). A total of 243 patients with CRC were enrolled and defined as pMMR (121 patients) or dMMR (122 patients). Using Pearson's χ test and multivariable multinomial logistic regression analysis, the associations between MMR status, TIL presence and PD-L1 expression were investigated, in addition to the association between TIL/PD-L1 status and clinicopathological features. The results demonstrated that the dMMR group more frequently exhibited TIL (85/122 vs. 61/121) and PD-L1 (49/122 vs. 32/121) phenotypes compared with the pMMR group. PD-L1 expression was identified in 42.4% of TIL cases in the dMMR group, while only 18.0% of TIL cases were PD-L1 in the pMMR group. High programmed death-1 expression and dMMR status were revealed as two independent risk factors for TIL PD-L1 status. In conclusion, compared with the pMMR group, the dMMR group was more likely to present with a TIL PD-L1 status, which suggests that a TIL PD-L1 tumor microenvironment may partly contribute to the improved response of dMMR patients to anti-PD-1/L1 therapy.
根据肿瘤浸润淋巴细胞(TILs)的有无和程序性死亡配体-1(PD-L1)表达对肿瘤微环境进行分类,已被用于预测免疫检查点抑制剂抗体在几种癌症类型中的疗效,但不包括结直肠癌(CRC)。本研究调查了CRC患者,特别是错配修复功能正常(pMMR)和错配修复缺陷(dMMR)患者的TIL/PD-L1状态。共纳入243例CRC患者,并将其定义为pMMR(121例患者)或dMMR(122例患者)。使用Pearson卡方检验和多变量多项逻辑回归分析,研究了错配修复状态、TIL存在与PD-L1表达之间的关联,以及TIL/PD-L1状态与临床病理特征之间的关联。结果表明,与pMMR组相比,dMMR组更频繁地表现出TIL(85/122 vs. 61/121)和PD-L1(49/122 vs. 32/121)表型。在dMMR组中,42.4%的TIL病例检测到PD-L1表达,而在pMMR组中,只有18.0%的TIL病例为PD-L1阳性。高程序性死亡-1表达和dMMR状态被揭示为TIL PD-L1状态的两个独立危险因素。总之,与pMMR组相比,dMMR组更有可能呈现TIL PD-L1状态,这表明TIL PD-L1肿瘤微环境可能部分有助于dMMR患者对抗PD-1/L1治疗的反应改善。