Mechanisms of immune response regulation in lung cancer.

Lung cancer is a leading cause of cancer deaths. As a solid tumor with low antigenicity and heterogenic phenotype lung cancer evades host immune defense. The cytotoxic anticancer effect is suppressed by a complex mechanism in tumor microenvironment. The population of regulatory T cells (Tregs) plays a crucial role in this inhibition of immune response. Tregs are defined by presence of forkhead box P3 (Foxp3) molecule. The high expression of Foxp3 was found in lung cancer cells and in tumor infiltrating lymphocytes (TIL). Cytotoxic T-lymphocyte antigen 4 (CTLA4) is constitutively expressed on Tregs and suppresses T cell activation. The elevated CTLA4 expression in lymphocytes in patients with lung cancer was found. Recently the antibodies blocking CTLA4 showed some clinical efficacy in patients with lung cancer. Cancer cells and immune cells release many cytokines capable to show suppressive immune effect in cancer microenvironment. The most active are transforming growth factorβ (TGFβ) and IL-10. The pleiotropic function of Th17 population is TGFβ related. The myeloid lineage of suppressor cells in lung cancer is represented by tumor associated macrophages (TAM) with phenotype of M2 macrophages and some regulatory properties with releasing amounts of IL-10 and TGFβ. The myeloid derived suppressor cells (MDSCs) control cytotoxic T cell activity in mechanisms which are highly dependent on the context of tumor environment. The mechanisms of anticancer immune response regulation need further investigation as an important target to new way of treatment.