The effect of mediastinal lymph node dissection on inhibitory receptor expression of cytotoxic T lymphocyte in non-small cell lung cancer patients

Non-small cell lung cancer (NSCLC) is leading cause of cancer-related death. Video-assisted mediastinoscopic lymphadenectomy (VAMLA) increases survival. We evaluated the phenotype and function of ctytotoxic T cells (Tc) in NSCLC patients, who underwent VAMLA. We included 17 T1-4N0-2M0 NSCLC patients and 20 healthy subjects. Preoperative peripheral blood, lymph node (LN), postoperative 2nd-week blood samples were taken in patients. Healthy subjects donated one blood sample. PD1, CTLA-4 and CD28 expression, TNF- & IFN- secretion, and cytotoxic activity of Tc lymphocytes were evaluated by flow-cytometry. sPD-1, sPDL-1 and sCTLA-4 was measured with ELISA. In LN Tc cells; CTLA-4, PD-1 expression was increased; the ratio of CD8+CD28- inhibitor cells was lower and CD8+CD28+ activator cells was higher compared to blood. In NSCLC, the ratio of CD3+CD8+CD28+ cells was lower and CD3+CD8+CD28- cells was higher in blood. After VAMLA, expression of PD-1 and CTLA-4 was reduced in blood Tc, but CD28 expression and cytokine secretion remained unchanged. The ratio of TNF- and IFN-+TNF-+ expressing Tc cells was significantly-lower in LN compared to blood. CTLA-4 expressing Tc cells secreted less IFN- and TNF- Granzyme A secretion was lower in blood Tc cells in NSCLC, but granzyme A expression increased after VAMLA. Plasma sCTLA-4 levels were higher in NSCLC. The effector functions of CD8+ Tc cells are reduced and suppressive phenotype is increased in tumor-draining lymph nodes. After VAMLA, the functional loss in Tc cells improved along with a decrease of PD-1 and CTLA-4 expression. This effect of VAMLA on Tc cells might contribute to its effect on survival rates. Key Words: Cytotoxic T cells, NSCLC, VAMLA, lymph node, PD-1, CTLA-4.