The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and strom
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The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression Florent Petitprez1,2,3* , Sacha Levy1†, Cheng-Ming Sun1†, Maxime Meylan1,2†, Christophe Linhard1, Etienne Becht4, Nabila Elarouci2, David Tavel2, Lubka T. Roumenina1, Mira Ayadi2, Catherine Sautès-Fridman1, Wolf H. Fridman1† and Aurélien de Reyniès2*†
Abstract Quantifying tissue-infiltrating immune and stromal cells provides clinically relevant information for various diseases. While numerous methods can quantify immune or stromal cells in human tissue samples from transcriptomic data, few are available for mouse studies. We introduce murine Microenvironment Cell Population counter (mMCPcounter), a method based on highly specific transcriptomic markers that accurately quantify 16 immune and stromal murine cell populations. We validated mMCP-counter with flow cytometry data and showed that mMCPcounter outperforms existing methods. We showed that mMCP-counter scores are predictive of response to immune checkpoint blockade in cancer mouse models and identify early immune impacts of Alzheimer’s disease. Keywords: Immune composition, Heterogeneous tissue, Tumor microenvironment, Immune checkpoint blockade, Alzheimer’s disease
Background For a large number of diseases, such as inflammatory diseases or cancer, it is often crucial to accurately determine the cellular composition of the tissue where the pathology develops, in terms of immune and stromal cell * Correspondence: [email protected]; [email protected] † Sacha Levy, Cheng-Ming Sun and Maxime Meylan contributed equally to this work. † Wolf H. Fridman and Aurélien de Reyniès are co-senior authors. 1 Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Team Inflammation, Complement and Cancer, F-75006 Paris, France 2 Programme Cartes d’Identité des Tumeurs, Ligue Nationale contre le Cancer, F-75013 Paris, France Full list of author information is available at the end of the article
populations. An array of methods are available to obtain these data from human samples, either by immunochemistry or cytometry, or computationally from transcriptomics data [1]. The analysis of the immune and stromal composition of tissues is particularly critical in cancer studies. Indeed, tumors are highly heterogeneous tissues which are infiltrated by a variety of immune and stromal cells [2]. It was shown that immune cell densities were associated with prognosis [3]. For instance, CD8+ T cells density correlates with prolonged patient survival in most cancers, whereas M2-polarized macrophages are generally associated with a poor prognosis [3].
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the
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