Escape from immune surveillance is an important feature of cancer. Most patients with advanced lung cancer do not respond to treatment by blocking the PD-1/PD-L1 control pathway, highlighting the need to identify new targets for immune checkpoint inhibition or regulation. 

The aim of the study was to evaluate CD137/CD137L and CD200/CD200L expression on the tumor cells and lymphocytes in lymph node (LN) aspirates obtained during EBUS/TBNA procedure of lung cancer patients.

Connection between the levels of antigens expression on cancer cells and the levels of antigens expression on lymphocytes were analyzed by multiparameter flow cytometry (FC). Presence of neoplastic cells was analyzed using cytology, hematology analyzer and FC.

The tumor cells showed a high expression of EpCAM and cytokeratin (respectively 81.9% and 78.8%). CD137L expression was observed mainly on the tumor cells (53.6%) and also on the lymphocytes among a few cases (15.2%). Lymphocytes had very low expression of CD137 (1.7%). CD200 expression was observed on both the tumor cells and lymphocytes. CD200L expression was higher on the tumor (21.3%) than on lymphocytes (10.3%). High tumoral CD137L expression was positively linked with cytokeratin and PD-L2.  Meanwhile, high tumoral PD-L1 expression was negative correlated with CD137 expression on lymphocytes and CD200 on tumor cells. CD200L was positively significantly correlated with PD-L2 expression and CD137L expression on tumor cells.

We confirmed the association between the known immune checkpoint and novel pathways, which is an additional potential target for lung cancer patients and indicates the usefulness of assessing these elements in diagnosis.