Gastric Cancer Immunotherapy: An Overview

Gastric adenocarcinoma is the third most common cancer and the second most common cause of death due to cancer worldwide. Surgery is still the major prognostic factor for gastric cancer. Patients who could not be resected have a poor prognosis with survival ranging from 3 to 11 months. There is evidence that surgical operations can cause a variety of immunological disturbances in man both in vivo and in vitro. The postoperative changes in the systemic immune response are proportional to the degree of surgical trauma leading to a generalized state of immunosuppression, which is implicated in the development of septic complications and provided a “fertile soil” for tumor cell metastasis. Immunotherapy may be a potentially promising alternative strategy for gastric cancer. In early clinical trials, systemic immunotherapy included both active vaccination directed against defined tumor-associated antigens expressed in gastric carcinoma cells and passive administration of IL-2 with some evidence of regression of metastatic gastric cancer. Other studies have applied immunotherapy in the adjuvant setting with equally promising results. For example, OK-432, a streptococcal preparation, demonstrated marginal improvement in survival for patients with stage III gastric cancer and a meta-analysis of centrally randomized controlled clinical trials indicated a significant survival benefit with combination OK-432 and chemotherapy compared to chemotherapy alone (p < 0.05). Additional data suggesting a biological and clinical benefit of subcutaneous, preoperative administration of low-dose IL-2 in colon cancer encouraged us to evaluate low-dose IL-2 therapy in the neoadjuvant setting for patients with gastric adenocarcinoma who undergo surgery and to evaluate its effects on systemic and tumor infiltrating lymphocyte numbers. We also sought to determine if neoadjuvant low-dose IL-2 could influence the clinical outcome for patients undergoing gastric resection for cancer. We report the biological, histological and clinical results with the full accrual of patients and a median follow-up of 51 months.