Abstract 2946: Prognostic effect of tumor-infiltrating immune cell composition in non-small cell lung cancer by histology
Authors: Tamminga Menno , Hiltermann T. Jeroen , Schuuring Ed , Fehrmann Rudolf S. , Groen Harry J. 
Published: July 2017

Abstract
Introduction: The immune system plays an important role in tumor progression and treatment response, for example with the new immune modulating therapies. In lung cancer the effect of the individual immune cell types is unclear. In our study, we used publicly available expression data to find evidence whether there are differences in the composition of immune cell fractions within the microenvironment between squamous cell carcinoma and adenocarcinoma of the lung.
Methods: We searched the Gene Expression Omnibus (GEO) for human 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: Comparing the immune cell composition of adenocarcinoma (n=587) and squamous cell carcinoma (n=254), we observed in adenocarcinoma increased percentages of naïve and memory B-cells, resting and active CD4+ T-cells, regulatory T-cells, active NK cells, monocytes, M2 macrophages, resting dendritic cells and resting mast cells, and decreased percentages of plasma cells , CD8+ T-cells, follicular helper cells, resting NK cells, gamma delta T-cells, M0 and M1 macrophages and active mast cells. In adenocarcinoma, a higher percentage of memory B-cells in the immune infiltrate was associated with increased survival (HR 0.97, 95% CI 0.95-0.99, p=0.02), while higher percentages of neutrophils (HR of 1.07, 95% CI 1.01-1.13, p=0.02), M0 macrophages (1.02, 95% CI 1.01-1.04, p=0.01) and follicular helper cells (1.07, 95% CI 1.02-1.13, p=0.01) were associated with a worse survival. In both histologies, the resting mast cell immune fraction showed a positive association with survival (adenocarcinoma HR 0.96, 95% CI 0.93-0.99, squamous cell carcinoma HR 0.93, 95% CI 0.89-0.98, p&lt;0.01 in both histologies).In squamous cell carcinoma, a borderline association with a worse prognosis was observed with the naïve CD4+ T-cell fraction (HR of 1.1, 95% CI 1.00-1.22, p=0.053) and the regulatory T-cell fraction (HR of 1.11, 95% CI 0.99-1.24, p=0.067).
Conclusion: In NSCLC significant differences in intratumoral immune cell composition were observed between adenocarcinoma and squamous cell carcinoma.
Citation Format: Menno Tamminga, T. Jeroen Hiltermann, Ed Schuuring, Rudolf S. Fehrmann, Harry J. Groen. Prognostic effect of tumor-infiltrating immune cell composition in non-small cell lung cancer by histology [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 2946. doi:10.1158/1538-7445.AM2017-2946