Immunomodulatory and immunotherapeutic implications of tobacco smoking in squamous cell carcinomas and normal airway epithelium

The cover for issue 39 of Oncotarget features Figure 1, "The association of smoking history with immune infiltration and T cell activation in non-cancerous bronchial epithelium demonstrates stepwise immunosuppression with increasing smoking history," by Wang, et al.

The mutagenic effects of tobacco smoking increases the risk of the development of cancers of the lung, head and neck, and other anatomic sites.

In a comparison of squamous cell carcinomas of the lung and the head and neck, the researchers found that the immunomodulatory effects of smoking differ based on anatomic site.

The study was led by Dr. Jingming Wang, a postdoctoral fellow at Memorial Sloan Kettering Cancer Center in New York, NY, USA, working with Drs. Luc Morris and Timothy Chan from the Immunogenomics Precision Oncology Platform. Dr Wang explained, "Traditionally, cancers have been categorized by features such as anatomic site and tissue histology."

The likelihood of a tumor responding to immunotherapy treatments such as immune checkpoint blockade is known to be affected by these same factors, namely tumor mutational burden and the degree of immune infiltration in the tumor microenvironment.

In order to understand how tobacco smoking affects the tumor immune microenvironment and potentially identify the biomarkers to guide treatment options, the authors analyzed RNA and DNA sequencing data from cases studied as part of The Cancer Genome Atlas , as well as two independent gene expression datasets of lung squamous cell carcinoma and HNSC tumors .

They then examined the association between the mutational signature of smoking and RNA sequencing-derived measures of tumor immune infiltration and T cell activation.

In LUSC, a higher mutational smoking signature was positively associated with levels of immune infiltration, cytolytic activity and interferon- pathway signaling, indicating that smoking was associated with a more inflamed tumor immune microenvironment.

The Chan/Morris Research Team concluded, "Together with TMB, PD-L1 staining, measures of immune infiltration, HLA status, and other factors, it is likely that smoking history and/or the smoking mutational signature will add predictive value to our efforts to define biomarkers of response to ICB."

Full text - https://www.oncotarget.com/article/26982/text/

Correspondence to - Timothy A. Chan - [email protected] and Luc G.T. Morris - [email protected]

Keywords - immune, microenvironment