Meta-analysis of organ-specific differences in the structure of the immune infiltrate in major malignancies

// Gautier Stoll 1,2,3,4 , Gabriela Bindea 1,3,4 , Bernhard Mlecnik 1,3,4 , Jérôme Galon 1,3,4 , Laurence Zitvogel 5,6,7,8,9 and Guido Kroemer 1,2,3,4,5,10 1 Université Paris Descartes, Sorbonne Paris Cité, Paris, France 2 Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France 3 Institut National de la Santé et de la Recherche Médicale, Paris, France 4 Université Pierre et Marie Curie, Paris, France 5 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France 6 Institut National de la Santé et de la Recherche Médicale, Equipe labellisée Ligue Nationale Contre le Cancer, Villejuif, France 7 Institut Gustave Roussy Cancer Campus, Villejuif, France 8 Faculty of Medicine, University of Paris Sud, Kremlin-Bicêtre, France 9 Center of Clinical Investigations in Biotherapies of Cancer (CICBT), Villejuif, France 10 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France Correspondence to: Guido Kroemer, email: // Keywords : meta-analysis of microarrays, breast cancer, colorectal carcinoma, melanoma, non-small cell lung cancer Received : April 30, 2015 Accepted : May 09, 2015 Published : May 19, 2015 Abstract Anticancer immunosurveillance is one of the major endogenous breaks of tumor progression. Here, we analyzed gene expression pattern indicative of the presence of distinct leukocyte subtypes within four cancer types (breast cancer, colorectal carcinoma, melanoma, and non-small cell lung cancer) and 20 different microarray datasets corresponding to a total of 3471 patients. Multiple metagenes reflecting the presence of such immune cell subtypes were highly reproducible across distinct cohorts. Nonetheless, there were sizable differences in the correlation patterns among such immune-relevant metagenes across distinct malignancies. The reproducibility of the correlations among immune-relevant metagenes was highest in breast cancer (followed by colorectal cancer, non-small cell lung cancer and melanoma), reflecting the fact that mammary carcinoma has an intrinsically better prognosis than the three other malignancies. Among breast cancer patients, we found that the expression of a lysosomal enzyme-related metagene centered around ASAH1 (which codes for N-acylsphingosine amidohydrolase-1, also called acid ceramidase) exhibited a higher correlation with multiple immune-relevant metagenes in patients that responded to neoadjuvant chemotherapy than in non-responders. Altogether, this meta-analysis revealed novel organ-specific features of the immune infiltrate in distinct cancer types, as well as a strategy for defining new prognostic biomarkers.