Tumor immunotherapy of esophageal and gastric cancers

Abstract

Esophageal and gastric cancers are prevalent and heterogeneous diseases that require patient-specific treatments. Over the past two decades, multidisciplinary approaches have contributed to the development of novel treatments that have significantly improved prognoses. Despite these advancements, survival rates remain low, and novel treatment strategies are required to improve the clinical outcome. The therapeutic potential of cancer immunotherapy has only recently been realized in several cancers, including refractory cancers of the GI tract. Similarly, esophageal and gastric cancers are also amenable to immunotherapy since patients often contain naturally occurring HLA class I-restricted cytotoxic T lymphocytes (CTLs) that specifically target tumor-associated antigens. Prompted by the insights derived from studying these tumor-specific CTLs, therapeutic strategies are currently being developed. This chapter reviews the promising strategies that employ monoclonal antibodies, adoptive cell transfer, and vaccine-based immunotherapy for the treatment of esophageal and gastric cancers. To date, several cancer vaccine trials have been performed in patients with advanced esophageal and gastric cancers. Here, we summarize data from these phase I or phase II clinical trials. For example, a recent phase II trial revealed that vaccination with peptides derived from testicular cancer-specific antigens could improve the prognosis of patients with advanced esophageal cancer. In addition, we describe a novel immunotherapeutic approach, called personalized peptide vaccine (PPV), in which HLA-matched peptides are selected and administered based on preexisting host immunity. Further clinical trials are required to assess the clinical benefits of these immunotherapeutic approaches.