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Mark, NM; Kargl, J; Busch, SE; Yang, GHY; Metz, HE; Zhang, H; Hubbard, JJ; Pipavath, SNJ; Madtes, DK; Houghton, AM.
COPD Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in NSCLC.
Am J Respir Crit Care Med. 2017;
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Autor/innen der Med Uni Graz:
Kargl Julia Katharina
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Abstract:
Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC. A murine cigarette smoke exposure model was used to evaluate the effect on pulmonary immune populations. A separate retrospective cohort of patients who received immune checkpoint inhibitors (ICIs) was analyzed and survival quantified. We observed an increased numbers of lymphocytes in the lungs of patients with COPD, consisting of increased IFN producing CD8+ and CD4+ (Th1) lymphocytes. In both humans and mice, Th17 content was seen with smoke exposure but was not associated with the development or severity of COPD. COPD-affected lung displayed increased Th1 differentiation that was recapitulated in the matching tumor sample. PD-1 expression was increased in tumors of patients with COPD, and the presence of COPD improved the progression free survival interval in patients treated with ICIs. In patients with COPD, Th1 cells populations were expanded in both lungs and tumors microenvironments, and the presence of COPD was associated with longer progression free interval in patients treated with ICIs. This has implications for understanding the immune mediators of COPD and for developing novel therapies for NSCLC.

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