Immunotherapy of Esophagus Cancer

Esophageal carcinoma (EC) is one of the most aggressive cancer types in the world and is on the rise in incumbrance in several countries. Esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) are the two most common histological types of EC which present with unique epidemiological distributions and molecular characteristics. Traditional treatment approaches have limited outcomes with advanced cancer, prompting exploration for newer treatments on a novel basis. Immunotherapy was developed as an effective treatment intervention to utilize the individual's immunologic response to locate and destroy malignant cells. This paper will review recent studies and publications on immunotherapy-based treatment approaches for esophagus cancer related to immune checkpoint inhibitors (ICIs), adoptive cell therapies, and new combination treatment approaches; plus clinical trials. Clinical trials reported recently, have shown ICIs as an effective anti-cancer option for esophageal cancer: ۱. KEYNOTE-۱۸۱: This phase III RCT looked at pembrolizumab in advanced EC and former chemotherapy patients. The evidence indicated overall survival (OS) benefits in patients with high PD-L۱ compared to a normal chemotherapy regimen. ۲. CheckMate ۵۷۷: This phase II RCT looked at nivolumab in patients with residual disease after definitive chemoradiotherapy. The evidence indicated significant monitoring and survival benefits. Nivolumab had a significant (DFS) distinction, especially in ESCC. ۳. ATTRACTION-۳: This RCT compared patients with nivolumab versus chemotherapy in previously treated advanced ESCC. ORs favored nivolumab which was superior to chemotherapy previously. Adoptive cell therapy, especially CAR T-cell therapy is currently being assessed as a potential treatment modality for esophageal cancer. While promising, this evidence must undergo a larger trial protocol to adequately determine effectiveness and safety. The approach of combining immunotherapy with chemotherapy or targeted therapies is an exciting area of research. Evidence has emerged that some combinations offer better response rates and can target resistance mechanisms. Early phase trials are trialing these options. The use of predictive biomarkers to characterize patients remains an important area of interest. For now, PD-L۱ expression remains the most studied predictive biomarker, and tumor mutational burden (TMB) and microsatellite instability (MSI) are also being investigated. Immunotherapy represents a significant advance in the treatment of esophageal cancer through immune checkpoint inhibitors such as pembrolizumab and nivolumab and enhanced survival has been demonstrated in some trials. However, biomarker progress and adverse events remain common challenges. More research is needed to refine these therapies and assess any combination strategies that may confer a higher response rate. As we increase our understanding of the immunological landscape of esophageal cancer, there is an opportunity to assess immunotherapeutics focused on personalization to improve overall survival and or quality of life for patients.

کلیدواژه ها:

Esophageal Cancer ، Immunotherapy ، Immune Checkpoint Inhibitors ، Adoptive Cell Therapy