PD-L2: A prognostic marker in chromophobe renal cell carcinoma?

Abstract

In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for PD-L2 expression by immunohistochemistry. Expression data were associated with clinicopathological parameters and overall survival (OS). Twenty-three (28.4%) patients showed a PD-L2 > median (PD-L2 high) staining intensity. No significant association between clinicopathological parameters and PD-L2 expression was identified. A significant difference between 5- and 10-year OS in dependence of PD-L2 expression was found (PD-L2 low 96.4 and 87.7% vs. PD-L2 high 87.1 and 56%; log rank, p = 0.029). However, in multivariate analysis PD-L2 expression failed to be proofed as an independent prognostic factor. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of PD-L2 in a considerably large cohort of chRCC. Our results showed a significant diminished OS in dependence of PD-L2 expression. This implicates that PD-L2 might play a role as prognostic marker in chRCC demanding further evaluation.

PD-L2 expression is correlated with the molecular and clinical features of glioma, and acts as an unfavorable prognostic factor

“…L2 positivelyrelated genes mainly focused on immune response (FDR = 1.63E-21, Benjamini = 2.29E-21), positive regulation of T cell proliferation function (FDR = 2.01E-04, Benjamini = 1.88E-05), defense response to virus (FDR = 3.50E-08, Benjamini = 7.02E-09), cytokine secretion (FDR = 0.001234438, Benjamini = 9.63E-05), positively regulation of NF-kappaB signaling(FDR = 6.33E-05, Benjamini = 6.84E-06) and cellular response to mechanical stimulus(FDR = 0.001, Benjamini = 1.12E-04) (Figure 3(a), 3 (b)). While negatively genes were mainly involved in physiological function, such as synapse and postsynaptic protein.In consistence with other malignant tumors,19,20 these results indicated that PD-L2 mainly probably played an important role in immunologic biological processes of host immune system in glioma.…”

The prevalence and prognostic and clinicopathological value of PD-L1 and PD-L2 in renal cell carcinoma patients: a systematic review and meta-analysis involving 3,389 patients

“…In the remaining 94 records, 78 of records were excluded because they were study samples, not published in English, or did not have sufficient information for OS, PFS, DFS, or relapse-free survival (RFS) calculation. After screening for the form of data reporting, 16 retrospective cohort studies (3,389 patients) (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were pooled in the final meta-analysis (shown in Figure 1).…”

ANO9 regulates PD‐L2 expression and binding ability to PD‐1 in gastric cancer

“…Programmed cell death 1 ligand 2 (PD‐L2) is a cell surface protein that has been detected in some cancers including colorectal cancer, 11,12 esophageal cancer, 13,14 GC, 15,16 hepatocellular carcinoma, 17,18 breast cancer, 19 and renal cell carcinoma 20 and regulates immune responses in cancer. Previous studies have suggested that programmed cell death 1 ligand 1 (PD‐L1) was the only ligand for programmed cell death‐1 (PD‐1).…”

“…cancer, 19 and renal cell carcinoma 20 and regulates immune responses in cancer. Previous studies have suggested that programmed cell death 1 ligand 1 (PD-L1) was the only ligand for programmed cell death-1 (PD-1).…”