Immune Checkpoint Therapy in Esophageal and Gastric Cancer

Introduction to Esophageal and Gastric Cancer

Esophageal and gastric cancer (GC) are both common and deadly; they can represent a major global health burden. GC is the fifth common cancer as well as the third leading cause of global cancer mortality. More disappointedly, the prognosis of advanced GC remains poor, with a median overall survival (OS) of 8-14 months. There are two major histological subtypes for esophageal cancer: squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). With an awful prognosis and poor therapeutic options, novel approaches are needed, and the interest in the impact of immunotherapy is increasing.

Fig.1 Immune checkpoint blockade in central and peripheral immune compartments. (Raufi, 2015)

Immune Checkpoint Inhibitors (ICIs) against Esophageal and Gastric Cancer

As the most classical immune checkpoint, PD-L1 is widely expressed in many human cancer cells. Some studies have shown that the PD-L1 overexpression in advanced gastric adenocarcinomas reached a 40% rate. In gastric cancer, the expression of PD-1 on CD8⁺ lymphocytes is significantly higher than that of normal gastric mucosa and peripheral blood.

Recent research has shown that the expression of B7-H4 is positively correlated with the invasion and metastasis of gastric cancer. Besides, gastric cancer patients with higher B7-H4 expression present a reduced median overall survival. The higher levels of expression of PD-L1 and PD-L2 have been served as the negative prognostic markers in esophageal cancer. Recently, some B7-H4 drugs have contributed to the approval of ICIs in the third-line treatment of advanced esophageal and gastric cancer. However, approximately 10% of ICIs-treated patients with esophageal and gastric cancer develop hyperprogression and lead to a dismal prognosis. In conclusion, the potential synergistic effect of combining radiotherapy, chemotherapy, and immune treatment is also future research directions.

Fig.2 Four molecular subtypes of GC/GEJC proposed by the Cancer Genome Atlas Research Network. (Zhang, 2020)

Services at Creative Biolabs

Creative Biolabs is a leading service provider that focuses on immune checkpoint therapy against esophageal and gastric cancer. Based on our extensive experience in drug discovery, now we can provide a series of services for our clients all over the world, which include but not limited to:

• Immune Checkpoint Antibody Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Immune Checkpoint Assays
• Custom Immune Checkpoint Protein Development
• Immune Checkpoint Targeted Peptide Development
• Preclinical Research for Immune Checkpoint Drugs

If you are interested in our services, please do not hesitate to contact us for more detailed information.

References

1. Raufi, A.; Klempner, S. Immunotherapy for advanced gastric and esophageal cancer: preclinical rationale and ongoing clinical investigations. Journal of gastrointestinal oncology. 2015, 6(5): 561.
2. Zhang, Z.; et al. Immune checkpoint inhibitors for treatment of advanced gastric or gastroesophageal junction cancer: Current evidence and future perspectives. Chinese Journal of Cancer Research. 2020, 32(3): 287.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.