Assessment of differences in the anti-tumor immune response between lung cancer patients with and without COPD.

Chronic obstructive pulmonary disease (COPD) has been consistently linked to lung cancer development. However, the precise mechanisms underlying this link are still incompletely understood. Preliminary observations obtained by genome-wide methylation profiling and wholetranscriptome sequencing of lung tumors suggest a weaker anti-tumor immune response in COPD versus non-COPD patients. This project therefore aims to establish differences in the immune response to lung tumors between patients with and without COPD. Specifically, we intend to confirm that COPD tumors are less infiltrated by immune cells as a sign of the impaired anti-tumor immune response in these patients. We will validate this finding by comparing the response of innate and adaptive immune cells to tumor cells in primary co-culture experiments and by assessing the specificity of tumor-infiltrating T-cells between COPD and non-COPD patients. In an attempt to redirect the anti-tumor immune response in COPD patients, we will seek for COPD-specific tumor antigens and evaluate whether these may be used to generate tumor-reactive T-cells. By also assessing the prognostic value of COPD and of a COPD-specific immune gene signature, we anticipate that this project will provide clinically relevant insights into the link between COPD and lung cancer. Additionally, our findings may stimulate efforts into developing specific immunotherapies targeted to lung cancer patients with COPD.