As a new nova of anti-tumor therapy, immunotherapy has been shown to be effective in many tumors of which PD-1/PD-L1 monoclonal antibodies has been proofed to increase overall survival rate in advanced gastric cancer (GC).
Summing up, heterogeneous or complete loss of ARID1A expression occurred in 14.7% of GCs and correlated with PD-L1 status, indicating potential for future combined anti-PD-L1/ARID1A therapy.
Immunohistochemistry was performed to detect HLA A/B/C, β2M, CD8, p53, and programmed death-ligand 1 (PD-L1) in the center and invasive margin of the tumor in 395 stage II and III GCs using tissue array method.
The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC).
From these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c-Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy.
However, the tumor microenvironment of gastric cancer is very complex and the association of PD-L1 with the tumor microenvironment in gastric cancer is still not clear.
In conclusion, HBV infection may contribute to a higher risk for GC based on the meta-analysis and to the morphological atypia of gastric epithelium by the histological assessment, and GC patients among HBV carriers showed lower expression of PD-L1 may lose the chance for immune checkpoint blockade therapy.
This suggests that the total number of PD-L1-expressing cells, including tumor and immune cells, is a more sensitive prognostic biomarker than the number of PD-L1-expressing tumor cells in GC.
<b>Conclusion:</b> PD-L1 monoclonal antibody-conjugated immunoliposomes have immense potential to be applied as a next-generation nanomedicine for PD-L1-positive gastric cancers.
The molecular subtype of gastric cancers is correlated with the immune subtype, including immune contexture and PD-L1 expression, within the tumor microenvironment.
Avelumab is a human IgG1 antibody directed against PD-L1 approved for Merkel cell carcinoma and urothelial carcinoma that could be useful also for the treatment of GC.
In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.