Functional evaluation of tumor‐infiltrating mononuclear cells. Detection of endogenous interferon‐γ and tumor necrosis factor‐α in human colorectal adenocarcinomas

Quantitative evaluation of the levels of interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) in the extracts of tumors and their corresponding normal tissues resected from 43 patients with colorectal adenocarcinoma was done using solid‐phase, sandwich radioimmunoassay. The levels of both IFN‐γ and TNF‐α detected in the tumor tissues were higher than those in the corresponding normal colorectal tissues obtained from each patient. A significant negative correlation was observed between the level of IFN‐γ and TNF‐α in each tumor extract. The decrease of the level of IFN‐γ in the tumor correlated with the advance of clinical stage, and the levels of IFN‐γ of the patients with distant metastases were significantly lower than those of the patients without distant metastases. However, an increase in the level of TNF‐α correlated not only with an enlarged diameter but also with the extent of the primary tumor. Immunohistochemical staining of IFN‐γ and TNF‐α producing cells in tumor tissues showed that IFN‐γ was mainly produced by CD4 + CD8– T‐lymphocytes and TNF‐α was mainly produced by CD11c+ cells with macrophage‐like morphology. These results suggest that CD4+ T‐lymphocytes that produce IFN‐γ might play an important role in the antitumor response against cancer progression in human colorectal adenocarcinomas.