Noh Byeong-Joo, Kwak Jae Young, Eom Dae-Woon
Department of Pathology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea.
Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea.
BMC Cancer. 2020 Jan 28;20(1):58. doi: 10.1186/s12885-020-6553-9.
Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancer-related death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapy-targetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup.
Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and deficient mismatch repair (dMMR) were performed and evaluated.
Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1-negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with dMMR status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression.
TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.
结直肠癌是全球第三大常见癌症，也是癌症相关死亡的主要原因。近来，多种免疫治疗药物的出现使得解读与肿瘤浸润免疫细胞交织在一起的复杂肿瘤微环境以预测免疫治疗反应率变得至关重要。然而，在结直肠癌中，缺乏对程序性死亡配体1（PD-L1）和肿瘤浸润淋巴细胞（TIL）进行详细分析以阐明其预后价值并识别免疫治疗可靶向亚组的研究，最好是有多个免疫相关生物标志物。在本研究中，我们根据PD-L1表达和TIL将结直肠癌分为四种肿瘤免疫微环境类型，分析它们的预后价值，并提出一个免疫治疗可靶向亚组。
获取手术切除的原发性结直肠癌（n = 489）的福尔马林固定、石蜡包埋组织样本，并将其排列在组织微阵列块上。进行并评估PD-L1、程序性细胞死亡蛋白1（PD-1）、分化簇8（CD8）和错配修复缺陷（dMMR）的免疫组织化学染色。
肿瘤微环境免疫类型（TMIT）I（PD-L1阳性肿瘤细胞和CD8高表达TIL）和类型II（PD-L1阴性肿瘤细胞和CD8低表达TIL）分别显示出最好和最差的预后。PD-L1过表达与dMMR状态显著相关。PD-L1免疫反应性与CD8或PD-1过表达的TIL呈正相关。
与其他TMIT相比，TMIT I亚组显示出更强的CD8/PD-L1/PD-1信号相互作用。因此，我们提出TMIT I亚组是预测现有免疫检查点抑制剂有效反应率并确定新兴疗法可靶向亚组的候选TMIT。
