Therapeutic strategies for gastric cancer targeting immune cells: Future directions

Abstract

Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte–associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell–based therapeutic methods will be developed and applied.

Identification and validation of a novel redox- related differentially expressed lncRNA prognostic signature for predicting clinical immunotherapy response in gastric cancer

“…Immune checkpoint inhibitors programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) antibodies, cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibodies, and chimeric antigen receptor T (CAR-T) in ACT. These therapeutic strategies have signi cant anti-tumor e cacy in solid and hematological tumors while targeting other immune cells offers a new direction for immunotherapy in GC 59 . In this study, patients in the high-risk group were signi cantly enriched for genes in immune-related pathways.…”

Perspectives for immunotherapy ofEBV‐associatedGLELC: A relatively “hot” tumor microenvironment

“…For advanced-stage GC, chemotherapy-based comprehensive treatment is the main treatment method. 9 However, for EBV-associated GLELC (EBVaGLELC), which is commonly reported in case reports and small series, there is no standard therapy, and practitioners lack a reference point for determining the treatment strategy. Immunotherapy, especially immune checkpoint inhibitors (ICIs), heralded a new era of advanced cancers, including gastric adenocarcinoma (GAC), [10][11][12][13][14] but the efficacy in EBVaGLELC has not been well characterized.…”

“…Most GC patients are not considered for surgery at the time of diagnosis. For advanced‐stage GC, chemotherapy‐based comprehensive treatment is the main treatment method 9 . However, for EBV‐associated GLELC (EBVaGLELC), which is commonly reported in case reports and small series, there is no standard therapy, and practitioners lack a reference point for determining the treatment strategy.…”

F-box and leucine-rich repeat 6 promotes gastric cancer progression via the promotion of epithelial-mesenchymal transition

“…Approximately 950000 new cases of patients with GC are diagnosed worldwide each year; however, a decline in incidence and mortality rates has been observed in recent years[ 3 ]. As traditional treatment strategies for gastric cancer, surgical resection, chemotherapy, and radiotherapy continue to show shortcomings; this is the main reason for the < 30% 5-year overall survival (OS) for patients with GC[ 4 , 5 ]. Therefore, further research is warranted to help researchers elucidate the underlying molecular mechanisms and identify effective therapeutic avenues to enhance survival in GC.…”