Dissociation between T helper type 1 and type 2 differentiation and cytokine production in tumor-infiltrating lymphocytes in patients with lung cancer.
We recently reported the balance of T helper type 1 (Th1) cells and type 2 (Th2) cells in patients with lung carcinomas. This study was conducted to investigate their activity and role in tumors, which remain unclear. We determined the population of lymphocytes with intracellular interferon (IFN)-gamma or interleukin (IL)-4 by flow cytometry, and investigated cytokine production using enzyme-linked immunosorbent assay (ELISA) in 22 patients with non-small cell lung cancer. The IFN-gamma-positive subset showed a significant increase in the number of tumor-infiltrating lymphocytes (TIL) compared with the peripheral blood lymphocytes (PBL) (PBL, 13.8% +/- 1.5%; TIL, 34.3% +/- 3.4%; P < 0.001), and the IL-4 positive subset showed reverse results (PBL, 3.7% +/- 0.6%; TIL, 2.1% +/- 0.3%; P = 0.037). However, TIL did not produce more IFN-gamma than PBL. The results of intracellular IFN-gamma analysis and the production of IFN-gamma in PBL and TIL were significantly correlated (PBL: n = 22, r = 0.50, P = 0.025; TIL: n = 22, r = 0.44, P = 0.022). The dissociation between Th1 differentiation and IFN-gamma production in TIL was one of the host factors influencing the immune anergy against tumors.