Clinicopathological significance and prognostic implication of programmed death-1 ligand 2 expression in colorectal cancer

Abstract

Purpose: The aim of this study was to evaluate the clinicopathological significance and prognostic role of programmed death-1 ligand 2 (PD-L2) expression in colorectal cancer according to intratumoral components. Methods: We used immunohistochemical analysis to investigate the impact of PD-L2 expression on clinicopathological characteristics and survival in 264 human colorectal cancer tissues. We also evaluated the correlation between PD-L2 expression and PD-L1 expression. Results: PD-L2 was expressed in 17.4% of the tumors (T-PD-L2) and in 19.3% of the immune cells (I-PD-L2) of the 264 CRC tissues. I-PD-L2 expression was significantly correlated with favorable tumor behaviors, including lower pathologic tumor stage, less lymph node metastasis, less distant metastasis, and lower pathologic tumor node metastasis stage. There was no significant correlation between I-PD-L2 expression and T-PD-L2 expression (P = 0.091). However, I-PD-L2 expression was correlated with PD-L1 expression in the immune cells (P < 0.001). There was also a significant correlation between high Immunoscore and I-PD-L2, but not T-PD-L2 (P < 0.001 and P = 0.190, respectively). The prognosis was better for patients who expressed I-PD-L2 than for patients who did not. In patients who expressed I-PD-L2, there was a significant difference in the survival rate between subgroups according to the presence or absence of T-PD-L2 expression. Conclusions: Our results suggest that I-PD-L2 expression is significantly correlated with favorable tumor behaviors and better survival rates. There is also a significant correlation between PD-L2 expression and PD-L1 expression in immune cells.

Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment

“…These findings are intuitively understandable, considering that PD-L2 expression suppresses tumor immunity as well as PD-L1 does. However, several studies have demonstrated that both PD-L2 and PD-L1 expression are favorable prognostic indicators for gastric and colorectal cancer[ 25 , 38 ]. To date, such discrepancies have been explained by differences in scoring methods, cutoff values of immunostaining, heterogeneities of carcinoma, and any bias originating from the inclusion of an insufficient number of cases.…”

Genes Involved in Immune Reinduction May Constitute Biomarkers of Response for Metastatic Melanoma Patients Treated with Targeted Therapy

“…The expression of PD-L1 in tissue does not seem to be a good biomarker in metastatic melanoma treated with targeted therapy [ 31 ], although its expression does increase in the microenvironment after the inhibition of BRAF, both in preclinical models and in tumour biopsies [ 32 , 33 ]. To our knowledge, no prior studies have been undertaken to determine PD-L1/PD-L2 in blood and to correlate their presence with the response to treatment for metastatic melanoma, although comparable studies have been conducted regarding other tumours [ 34 , 35 , 36 ]. Some papers have described the relation between PD-L2 expression and the presence of lymphatic metastases [ 37 ].…”

Prognostic relevance of programmed cell death 1 ligand 2 (PDCD1LG2/PD-L2) in patients with advanced stage colon carcinoma treated with chemotherapy

“…However, whether PD-L2 causes the immune suppression within the TME and its molecular mechanism require further investigation in the future. The association between PD-L2 expression and survival outcome has been investigated in several malignancies, including CRC, melanoma, pancreatic cancer, and esophageal cancer 33,[38][39][40][41] ; however, discrepancies between these studies have been observed. Several studies reported that high PD-L2 expression was associated with poor patient survival, including studies in esophageal cancer 32 , pancreatic ductal adenocarcinoma 42 and colorectal cancer 38,39 , and high tumor PD-L2 expression was associated with a favorable survival outcome in melanoma 40 and colorectal cancer 41 .…”