The predominant role of IL-6 in cancer is its key promotion of tumour growth. IL-6 binds IL-6 receptor (IL-6R) and the membrane-bound glycoprotein gp130. The complex I-6/IL-6R/gp130 starts the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3) or JAK/STAT3 pathway. IL-6R exits in two forms: a membrane-bound IL-6Rα subunit (mIL-6R) that participates in classic signalling pathway and soluble IL-6R subunit (sIL-6R) engaged in trans-signalling. The pro-tumour functions of IL-6 are associated with STAT3, a major oncogenic transcription factor that triggers up-regulation of target genes responsible for tumour cell survival. IL-6 combined with TGF-β induces proliferation of pathogenic Th17 cells. The anti-tumour function of IL-6 is the promotion of anti-tumour immunity. IL-6 trans-signaling contributed to transmigration of lymphocytes in high endothelial venules (HEV). Dendritic cell (DC) secreted IL-6 in the lymph node influences the activation, distribution and polarisation of the immune response. Elevated serum levels of IL-6 and increased expression of IL-6 in tumour tissue are negative prognostic marker for patients’ survival.
Gastric cancer (GC) is suitable for immunotherapy because 80% of it display microsatellite and chromosomal instability, some mutations and DNA hypermethylation. Therefore, GC is more immunogenic. The immunotherapy with monoclonal antibodies, adoptive cell therapy and checkpoint inhibition are discussed. The commonly used monoclonal antibodies are Trastuzumab targeting HER2 and Bevacizumab suppressing VEGF and tumor angiogenesis. Treatment with tumor-specific T cells is called adoptive cell therapy. There is experience with the application of tumor infiltrating lymphocytes (TILs), cytotoxic T lymphocytes (CTLs) and cytokine-induced killer cells (CIK). This review discusses the therapy with innate immune cells with anti-tumor activity such as dendritic cells and NK cells. The checkpoint inhibition was also reviewed. In conclusion, it could be stated that the immunotherapy of GC has the potential to provide a more favorable outcome to patients with GC, but it also have some limitations which need to be considered.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.