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.
By using a panel of PD-L1-expressing human GC cell lines and PD-L1-overexpressing cells, we studied cellular uptake, cytotoxic effects, and cellular apoptosis in the presence of PD-L1 mAb-conjugated NPs.
The molecular subtype of gastric cancers is correlated with the immune subtype, including immune contexture and PD-L1 expression, within the tumor microenvironment.
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).
We found that tumor PD-L1 positivity was associated with loss of ARID1A and showed trend toward better survival of patients with various molecular subtypes of GC (experimental set, n = 273).
<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.
PD-L1 membrane expression on tumour cells (TC) and infiltrating immune cells (IC), CD3 + T-lymphocytes, CD8+ cytotoxic T-cells, ATM and HER2 were assessed by immunohistochemistry (IHC) in the ACRG (Asian Cancer Research Group) GC cohort (N = 380).
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.
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.
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.
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.
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.