RRC ID 82682
Author Nakayama Y, Mimura K, Kua LF, Okayama H, Min AKT, Saito K, Hanayama H, Watanabe Y, Saito M, Momma T, Saze Z, Ohki S, Suzuki Y, Ichikawa D, Yong WP, Kono K.
Title Immune suppression caused by PD-L2 expression on tumor cells in gastric cancer.
Journal Gastric Cancer
Abstract BACKGROUND:Gastric cancer (GC) patients with PD-L1-negative tumor occasionally have a favorable response to anti-PD-1 mAb. The aim of the present study was to investigate the regulatory mechanism and immunosuppressive role of PD-L2 in GC.
METHODS:We used immunohistochemistry to evaluate the expression of PD-L2 in primary tumors from 194 patients with GC. The mechanism of PD-L2 expression was assessed in TCGA stomach adenocarcinoma tissue dataset and in vitro assay using GC cell lines. The immunosuppressive role of PD-L2 was evaluated by cytotoxicity of CTL clone against PD-L2 expressing GC cells.
RESULTS:PD-L2 was expressed on tumor cells (TCs) of 28.4% patients and PD-L2 expression on TCs was significantly associated with tumor progression. TCGA dataset revealed that IFN-γ and, to a lesser extent, IL-4 signature significantly correlated with PD-L2 expression. In vitro assay showed that IFN-γ and, also to a lesser extent, IL-4 can upregulate PD-L2 expression on GC cells. Anti-PD-L2 mAb significantly enhanced the cytotoxicity of CTL clone against GC cell lines expressing PD-L2.
CONCLUSIONS:PD-L2 is expressed on GC cells and PD-1/PD-L2 interaction are functionally involved in anti-tumor CTL activities. PD-L2 expression should be considered when determining the optimal immunotherapy for GC.
Volume 23(6)
Pages 961-973
Published 2020-11-1
DOI 10.1007/s10120-020-01079-z
PII 10.1007/s10120-020-01079-z
PMID 32367440
MeSH Cell Line, Tumor Gene Expression Regulation, Neoplastic / immunology* Humans Immunohistochemistry Immunosuppression Therapy / methods Immunosuppressive Agents / immunology* Programmed Cell Death 1 Ligand 2 Protein / immunology* Programmed Cell Death 1 Receptor / immunology Stomach Neoplasms / genetics* Stomach Neoplasms / immunology T-Lymphocytes, Cytotoxic / immunology*
Resource
Human and Animal Cells ECC10(RCB0983) GSU(RCB2278) HGC-27(RCB0500) KE-39(RCB1434) NUGC-4(RCB1939)