Inhibition of interleukin-2 dependent immune responses by serum from patients with advanced gastrointestinal cancer

Abstract

Immunotherapy with high-dose interleukin-2 (IL-2) fails to induce clinical responses in patients with advanced gastrointestinal cancer, but may be effective in patients with malignant melanoma or renal adenocarcinoma. The hypothesis that this failure may be related to immunosuppressive moieties present in patients with advanced gastrointestinal cancer was investigated. Serum samples from 93 patients (32 advanced gastrointestinal cancer, 22 localized gastrointestinal cancer, 13 melanoma/renal adenocarcinoma and 26 age-matched controls) were incubated with peripheral blood lymphocytes from healthy volunteers. The generation of cytolytic lymphokine-activated killer (LAK) cells and the allogeneic mixed lymphocyte response (MLR) were measured in-vitro. LAK effector cytotoxicity (mean % ± SEM) was significantly ( P < 0.05) decreased by serum from advanced gastrointestinal cancer patients (30 ± 3) compared with that from controls (47 ± 3), serum from patients with localized gastrointestinal cancer (49 ± 2) or that from patients with melanoma or renal adenocarcinoma (51 ± 2). MLR responses were also significantly ( P < 0.05) decreased using advanced gastrointestinal cancer patients serum compared to controls. A dose-response phenomenon for suppression of MLR was observed. Serum from patients with melanoma or renal adeno-carcinoma was not significantly different to control samples. The immunosuppressive properties of serum from patients with advanced gastrointestinal carcinoma may abrogate therapeutic attempts using IL-2.