Immune classification for the PD-L1 expression and tumour-infiltrating lymphocytes in colorectal adenocarcinoma

Abstract

Background: Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancerrelated 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 immunotherapytargetable 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. Methods: 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. Results: Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1negative 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. Conclusions: 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.

CD8+ Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma

“…This contrasts with known strong immunogenic tumours such as skin melanoma, renal cell and bladder cancer or head and neck and lung SCC, where TMIT I characterizes 40-50% of cases [21]. On the other hand, ITAC is comparable to adenocarcinomas of other organs such as lung, colon and stomach, with reports of 12-14%, 19% and 23% TMIT I, respectively [21,28,37,38].…”

Clinical Significance of a Novel Tumor Progression-Associated Immune Signature in Colorectal Adenocarcinoma

“…Responses to immune checkpoint inhibitors correlated with PD-L1 expression ( Salem et al, 2018 ). Studies have demonstrated that relatively high PD-L1 expression in cancer cells was associated with a good prognosis in CRC patients ( Wyss et al, 2019 ; Noh et al, 2020 ). The high expression of PD-L1 and CTLA4 in the low-risk group not only demonstrated that the IGBRS is an efficient classifier of risk stratification in CRC and closely related to tumor immunity but also suggested that the IGBRS may be a reference for the classification of CRC patients treated with immune checkpoint inhibitors.…”

Genomic landscape of ground glass opacities (GGOs) in East Asians

“…For profiling analysis of PD-L1 expression, the proportion of PD-L1-positive tumor cells (TCs) or immune cells were quantified. Light microscopy (20) was used for the semiquantitative assessment for PD-L1 immunoreactivity. Membranous immunostaining was interpreted according to the proportion and intensity of positive tumor cells.…”