Immunotherapy in Gastrointestinal Cancers

Abstract

Background: Gastrointestinal malignancies have both a high incidence rate and a high mortality rate. Immuno-oncological treatment approaches are becoming increasingly established in the treatment of gastrointestinal cancers. Summary: In this review, we give an overview of the types and effects of immunotherapies. We focus on recent studies on immunotherapies with special attention to immune checkpoint inhibition in carcinomas of the esophagus and stomach, the hepato-pancreatico-biliary system, and the colorectum including the anal channel in the metastatic setting, and we show their achievements but also their limitations. In an outlook, we discuss new approaches in immunotherapy like CAR T-cell therapy and oncolytic viruses. Key Messages: Gastrointestinal cancers show overall moderate response rates to immunotherapy. Nevertheless, subgroups such as DNA mismatch repair-deficient or microsatellite-instable tumors particularly benefit from the immune checkpoint blockade. Further studies are ongoing.

Clinical significance of peripheral T-cell receptor repertoire profiling and individualized nomograms in patients with gastrointestinal cancer treated with anti-programmed death 1 antibody

“…Recently, anti-PD-1 antibodies have been approved for the treatment of GICs, exhibiting encouraging outcomes ( 2 , 13 , 14 ). However, patients’ responses are often unpredictable.…”

“…The lack of effective early diagnosis and treatment strategies of GIC result in a poor prognosis. Currently, immunotherapy such as anti-programmed death 1 (PD-1) antibody has gained a significant value in the treatment of some GICs and has been incorporated into treatment regimens ( 2 ). However, a large number of patients do not respond to these treatment approaches, and toxicity may be substantial.…”

Vista of the Future: Novel Immunotherapy Based on the Human V-Set Immunoregulatory Receptor for Digestive System Tumors

“…Based on the CheckMate-040 clinical trial, the immunotherapy of hepatocellular carcinoma has been approved as a second-line treatment using nivolumab, a PD-1 inhibitor [ 17 ]. However, pancreatic cancer still lacks approved immunotherapy that would provide satisfactory effectiveness [ 18 ]. Lack of compromise on the immunotherapeutic approaches in GITs promotes the search for novel treatment strategies, especially considering the significant impact of TME and microbiota in tumorigenesis observed in these malignancies.…”

High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer

“…However, advances in molecular biology techniques allow us to approach an understanding of precise molecular mechanisms of carcinogenesis which holds promise for development of diagnostic, prognostic and therapeutic strategies. It is known that immune-related mechanisms and markers participate in the occurrence and development of GC and appropriately targeted therapy looks promising for its treatment (Güthle et al, 2020). Such observations highlight the urgent need to identify new immune-related biomarkers to facilitate early GC diagnosis and treatment.…”