Adenosine signaling: Optimal target for gastric cancer immunotherapy

Abstract

Gastric cancer (GC) is one of the most common malignancy and leading cause of cancer-related deaths worldwide. Due to asymptomatic or only nonspecific early symptoms, GC patients are usually in the advanced stage at first diagnosis and miss the best opportunity of treatment. Immunotherapies, especially immune checkpoint inhibitors (ICIs), have dramatically changed the landscape of available treatment options for advanced-stage cancer patients. However, with regards to existing ICIs, the clinical benefit of monotherapy for advanced gastric cancer (AGC) is quite limited. Therefore, it is urgent to explore an optimal target for the treatment of GC. In this review, we summarize the expression profiles and prognostic value of 20 common immune checkpoint-related genes in GC from Gene Expression Profiling Interactive Analysis (GEPIA) database, and then find that the adenosinergic pathway plays an indispensable role in the occurrence and development of GC. Moreover, we discuss the pathophysiological function of adenosinergic pathway in cancers. The accumulation of extracellular adenosine inhibits the normal function of immune effector cells and facilitate the effect of immunosuppressive cells to foster GC cells proliferation and migration. Finally, we provide insights into potential clinical application of adenosinergic-targeting therapies for GC patients.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

“…In addition, in the HERXO trial, trastuzumab combined with capecitabine and oxaliplatin were significantly effective in the treatment of advanced gastric cancer patients (mOS was 13.8 months vs 7.1 months), the 18-month disease-free survival (DFS) rate was 71% in perioperative treatment of gastric cancer[ 100 - 104 ]. The main results of trastuzumab combined with capecitabine and oxaliplatin in the treatment of advanced gastric cancer were consistent with those of the CGOG1001 trial[ 105 - 108 ]. The above results further established the basic position of trastuzumab in the first-line treatment of gastric cancer.…”

Targeting Immunosuppressive Adenosine Signaling: A Review of Potential Immunotherapy Combination Strategies

“…There is a wealth of both preclinical and clinical data that support further interrogation of adenosine signaling inhibition for numerous solid tumors. Adenosine signaling pathway components such as CD39, CD73, and A2 A receptors are overexpressed by multiple cell types in the TME of various cancers, including colorectal, gastric, head and neck, breast, and brain cancer, and often correlate with an immunosuppressive signature, aggressiveness, and poor prognosis in patients [44][45][46][47][48]. In 1975, Chu et al became the first to demonstrate that eADO could suppress T-cell activity against cancer cells in vitro [49].…”

Autologous CIK cells combined with chemotherapy as the first-line treatment for locally advanced or metastatic gastric cancer is safe and feasible

“…Its incidence ranks fifth in the world, while death rate ranks second, representing a serious threat to people's life and health (1). Surgical resection is the main radical treatment method for GC, although less than 50% of patients can achieve R0 resection (2). More than 80% of GC patients are in the advanced stage of the disease at the time of its discovery.…”