Abstract 4569: Effect of smoking on tumor-infiltrating immune cell composition and prognosis in non-small cell lung cancer
Authors: Tamminga Menno , Hiltermann T. Jeroen N. , Schuuring Ed , Fehrmann Rudolf S. , Groen Harry J. 
Published: July 2017

Introduction: The immune system plays an important role in tumor progression and treatment response such as with new immune modulating therapies. It is unclear in lung cancer what the effect of smoking is upon intratumoral immune cell composition and their function. In our study publicly available expression data were used to find evidence for the influence of smoking on the composition of intratumoral immune cell fractions and their prognostic impact.

Methods: We searched the Gene Expression Omnibus (GEO) for human non-small cell lung cancer (NSCLC) samples. Analysis was confined to samples hybridized to the Affymetrix HG-U133 Plus 2.0 (GEO accession number GPL570) platforms. Expression profiles were downloaded and curated for duplicates and corrupt files.

Different immune cell fractions were estimated using CIBERSORT and the LM22 leukocyte signature matrix. We combined this information with available clinical data. We used Cox regression analyses to evaluate the prognostic impact of the different immune fractions and Mann-Whitney U tests to test significant differences.

Results: Smokers with NSCLC had a significantly (p&lt;0.05) higher percentage of plasma cells, CD8+ T-cells, active CD4+ T-cells, follicular helper cells, monocytes, M0 macrophages, resting dendritic cells, active mast cells and neutrophils compared to non-smokers. Smokers had a lower percentage of naïve B-cells, memory B-cells, resting CD4+ T-cells and resting mast cells.

Non-smokers significantly benefit from a higher percentage of intratumoral memory B-cells in the immune infiltrate as compared to normal tissue (HR 0.92, 95% CI 0.85-1.00, p=0,049), while the smokers significantly benefit from higher intratumoral immune factions of resting CD4+ T-cells (HR 0.93, 95% CI 0.89-0.98, p=0.001). Higher percentages of regulatory T-cells (HR 1.23, 95% CI 1.03-1.47, p=0.025), neutrophils (HR 1.11, 95% CI 1.02-1.21, p=0.014) and follicular helper cells (HR 1.12, 95% CI 1.01-1.24, p=0.03) had a significant detrimental effect on survival of smokers.

There was a borderline beneficial effect for smokers of the intratumoral NK cell faction (HR 0.61, 95% CI 0.36-1.02, p=0.057). For non-smokers, a detrimental effect was observed for the intratumoral plasma cell fraction (HR 1.04, 95% CI 1.00-1.09, p=0.073) and the naïve B-cell fraction (HR 1.17, 95%CI 0.99-1.39, p=0.075).

Conclusion: In NSCLC significant different composition of intratumoral immune cells were observed between a smoking and non-smoking population. These differences were associated with differences in overall survival.

Citation Format: Menno Tamminga, T. Jeroen N. Hiltermann, Ed Schuuring, Rudolf S. Fehrmann, Harry J. Groen. Effect of smoking on tumor-infiltrating immune cell composition and prognosis in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4569. doi:10.1158/1538-7445.AM2017-4569