Do two lungs form an integrated immune system? Learning from BALF examination in lung cancer

Background: Bronchoalveolar lavage fluid (BALF) examination was found to be useful in the evaluation of local immune status in the site of lung cancer development. This procedure may be performed during lung cancer diagnosis and repeated during therapy. It especially concerns the majority of lung cancer cases, which are beyond the possibility of resection at recognition. However, the procedure of BAL in the lung affected by cancer is often complicated. The aim of this study was an analysis of differences in the character of immune response between the lung affected by cancer versus the opposite, 'healthy' lung. May BALF from the lung free of tumor serve for the characterization of local immune status? Methods: BALF of 36 patients was harvested from the lung affected by cancer and opposite site: the lung without tumor. BALF cells were analyzed by means of the following sets of antibodies anti: the first probe CD4, CD127, CD25, Foxp3, CTLA4, the second probe: CD3, CD16/CD56, CD45, CD19, CD8. For macrophage phenotyping the immunofluorescent method with antibodies anti: CCR7 and CD163 was used. The concentrations of 27 cytokines were analyzed in the duplicate using Bio-Plex Pro Human Cytokine Assay. The next part of the study was performed in other 32 patients by the same method with a panel of antibodies anti: CD3, CD4, CD8, CD127, CD45RA, CD69, CTLA-4, PD-1. Results: By the analysis of the BALF profile we found that only the cells and cytokines involved in regulatory pathways showed significant differences between both the 'healthy' and the cancerous lung, being elevated in the latter. The proportion of Tregs, CTLA4+Tregs, activated and memory PD-1+ lymphocytes, CCR7lowCD163high macrophages were significantly higher in the lung with cancer than in the healthy lung. On the other hand, the proportion of effectory cells and inflammatory cytokines concentration did not differ between both lungs, which may indicate that they form an integrated immune system and individual homeostasis. Conclusions: Regulatory mechanisms which are up-regulated in the tumourbearing lung affect BALF profile in the lung with cancer, while the examination of BALF from the "healthy" lung may serve for the evaluation of individual basic profile of the anti-cancer response. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: J. Domagala-Kulawik: Travel grant, consultant: BMS, MSD. All other authors have declared no conflicts of interest.