Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients.

The expression patterns of immunosuppressive molecules on regulatory T (Treg) cells have not been elucidated in non-small-cell lung cancer (NSCLC) patients. In this study, a total of 88 patients including 53 patients with NSCLC, 17 patients with lung non-malignant diseases, and 18 healthy volunteers were enrolled. Increased number of total CD4(+)CD25(+)FoxP3(+) Treg cells and elevated expressions on the surface of several inhibitory molecules including CTLA-4, LAG-3 and PD-1 have been observed in the peripheral blood of NSCLC patients. We found that intratumoral Treg cells from NSCLC patients express the highest levels of co-inhibitory molecules compared to Treg cells isolated from tumor adjacent tissues or from peripheral blood of cancer patients, which is in consistent with the enhanced immunosuppressive function of these co-inhibitory molecules. Moreover, the number of Treg cells and their functional surface molecules increased during the progression of lung cancer. Elevated plasma levels of TGF-β and IL-10 in NSCLC patients were also observed in NSCLC patients compared to that in healthy volunteers. Our findings further support the role of Treg cells in the tumor microenvironments in NSCLC patients.