Editors' ChoiceCancer

Through the smoke lies a further threat

See allHide authors and affiliations

Science Translational Medicine  25 Oct 2017:
Vol. 9, Issue 413, eaap8173
DOI: 10.1126/scitranslmed.aap8173

Abstract

CD4+ lymphocyte differentiation is enhanced in patients with concomitant COPD and lung cancer, improving responses to immune checkpoint inhibition.

The relationship between lung cancer and chronic obstructive pulmonary disease (COPD), the two major causes of smoking-related lung disease, extends beyond cigarette smoking. A diagnosis of COPD increases the risk for developing lung cancer, even after smoking cessation and adjusting for the effects of smoking alone. The synergy between these two diseases is poorly understood, but the adaptive immune response plays a key role in both and has provided the basis for emerging therapies against lung cancer. For example, inhibitors of the immune checkpoint programmed cell death 1 (PD-1), which exhibits increased expression in COPD and lung cancer, reactivate exhausted T cells and restore their antitumor activity.

Mark et al. aimed to clarify the role of the adaptive immune response in the interaction between lung cancer and COPD, profiling immune cell populations and focusing on immune checkpoints. The authors examined tumor and adjacent lung tissue of patients with and without COPD at the time of lung cancer resection, primarily using flow cytometry. Most notably, they found that interferon-γ producing CD8+ and CD4+ T cells (TH1) were increased in the lung tissue and tumor microenvironment in COPD, and that the CD4+ TH1 subtype was the immune cell population that was most strongly correlated between tumor and lung tissue. In addition, immune checkpoint expression, including PD-1, was enhanced in tumor samples from patients with COPD—but not in surrounding lung tissue—in contrast with previous reports. The investigators were unable to determine whether immune cell profiles were modified by COPD after lung cancer therapy with immune checkpoint inhibitors (ICIs) because they did not have the necessary samples. They did, however, find that a diagnosis of COPD improved lung cancer progression-free survival after ICI treatment in a retrospectively analyzed clinical study.

The results of immune cell profiling were necessarily confounded by the fact that all participants with COPD also had lung cancer, which could have modulated their immune response. However, this study provides an important step forward in unraveling the complicated interaction between these two diseases, which may improve our understanding of who will benefit from ICIs and how to harness the immune system to treat both diseases.

Highlighted Article

View Abstract

Navigate This Article