Analysis of the immunological microenvironment at the tumor site in patients with non-small cell lung cancer.

Abstract

Inactivation of tumor-infiltrating lymphocytes by immunomodulating cytokines shed by tumor cells into the tumor local microenvironment might be a potential escape strategy of various tumors from immune-immediate killing. Here, we provide an analysis of the cytokine profile at the tumor site in patients with non-small cell lung cancer (NSCLC). Using in situ hybridization (ISH), we determined the mRNA expression in lymphocytes and tumor cells for IL-2, INF-gamma, IL-12 (p40), IL-18, IL-4, IL-10, TGF-beta1, IL-1, IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-alpha, and TGF-alpha in five fresh pleural effusion samples and 18 tumor tissue samples of patients with NSCLC. In pleural effusion as well as in tumor tissue of NSCLC patients, the mRNA expression of IL-4, IL-10, TGF-alpha, and TGF-beta1 was significantly higher than that of IL-2, IL-12, IL-18 and INF-gamma. In contrast, the analysis of tuberculosis pleural effusion samples revealed lower mRNA levels for all cytokines and did not show any significant difference among them. The predominant mRNA expression of type II and immunosuppressive cytokines in pleural effusion and tumor tissue of NSCLC patients mirrors an immunosuppressive state in the immunological microenvironment. The present study may, therefore, help to elucidate mechanisms of tumor escape and contribute to the development of an effective immunomodulatory treatment of NSCLC.