Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer

Abstract

As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.

Visual analysis of global research on immunotherapy for gastric cancer: A literature mining from 2012 to 2022

“…ACI has proven to be an effective strategy for advanced GC 88 ，which is also the burst keywords. CAR-T, which appears all in the burst keywords and timeline view of co-cited references, is one of the hottest treatment modalities of ACI in recent years.…”

Immunoexpression of E-cadherin, CD44 and Claudin 7 in gastric adenocarcinomas

“…Gastric adenocarcinomas are responsible for 8.8% of the deaths caused by cancer worldwide and continue to represent a major problem globally [ 2 , 3 ]. The multifactorial etiology and heterogeneous clinico-pathological character are determinants for the aggressive biological behavior of the lesions [ 4 , 5 ]. Although the screening programs have decreased the incidence of the lesions, and the methods of diagnosis and treatment of gastric adenocarcinomas have been improved in recent years, the prognosis remains reserved and the mortality rate high.…”

“…Although the screening programs have decreased the incidence of the lesions, and the methods of diagnosis and treatment of gastric adenocarcinomas have been improved in recent years, the prognosis remains reserved and the mortality rate high. In the context of frequently discrete symptoms, most patients are diagnosed in advanced stages [ 5 , 6 ]. Therefore, there is a permanent concern for improving the prognosis of patients, existing numerous studies that have analyzed the biomolecular mechanisms involved in tumor initiation and progression.…”

Adenosine signaling: Optimal target for gastric cancer immunotherapy

“…As the disease progresses, hemorrhage, perforation, obstruction, cachexia, and other symptoms of advanced cancer gradually appear. GC is already in the advanced stage once detected in patients, which has a poor ending due to ineffective therapies and multiple resistance (6). Therefore, accurately diagnosing EGC and effectively treating advanced gastric cancer (AGC) patients who have lost the chance of radical surgical resection are two serious health problems all over the world.…”

“…As the most extensively used ICIs at present, checkpoint inhibitor-based immunotherapies that target the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway have achieved impressive success in the treatment of different cancer types (16). Nevertheless, there still exists various challenges that have severely limited the clinical application of immunotherapies in AGC, for instance, the ineffectiveness and serious side effects (6). For AGC patients, anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies cannot acquire satisfactory curative effect without the assistance of other cancer treatments (17-20).…”