Abstract
Considering the limited progress of chemotherapy and targeted therapy in improving the generally disappointing outcomes of advanced gastric or gastroesophageal junction cancer (GC/GEJC), immunotherapies have been gradually developed and advanced into novel frontiers of treatment for advanced GC/GEJC. Nevertheless, the response to immunotherapy was not always satisfactory, and the emergence of resistance was unavoidable. These factors prompt the development of different combination therapies and predictive and prognostic biomarkers of efficacy to improve the outcomes of patients with advanced GC/GEJC and to overcome drug resistance. This article discusses the advances of immune monotherapy, multiple current and ongoing clinical trials of immune combination therapy, immune-related adverse events, and various biomarkers in GC/GEJC.
Highlights
for more robust predictive biomarkers are essential for improving the treatment efficacy of patients
in our study center have confirmed the efficacy of immunotherapy combined with chemotherapy
that the clinical application of immunotherapy may be expanded to early-stage gastric cancer (GC)
Summary
Cancer vaccines take advantage of antigens associated with tumor cells such as proteins overexpressed in tumor cells, cancer-testis antigens (CTAs), protein products of oncogenes, and heat-shock protein complexes [10], which may be recognized as foreign by the host adaptive immune system and trigger antitumor immune responses [11]. MAGE-3 peptide vaccine acted as an adjuvant and was used to enhance an antitumor immune response resulting in a successful regression of tumor growth in a mouse model of GC [12]. A phase I trial assessed the efficacy of NY-ESO-1 vaccine in tumors where 9 out of 10 patients with gastroesophageal cancer had an enhanced antibody response, and all patients had an increase in antigen-responsive CD4 and CD8 T cells [14]. Heat shock proteins (HSP), acting as tumor rejection antigens, can form protein complexes with various deranged intracellular proteins and induce CD4+ and CD8+ T cell responses, suggesting that vaccines against HSP will play a role in immunotherapy for GC [16]
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