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Transcriptomic analysis of the tumor microenvironment to guide prognosis and immunotherapies

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Abstract

Tumors are highly heterogeneous tissues where malignant cells are surrounded by and interact with a complex tumor microenvironment (TME), notably composed of a wide variety of immune cells, as well as vessels and fibroblasts. As the dialectical influence between tumor cells and their TME is known to be clinically crucial, we need tools that allow us to study the cellular composition of the microenvironment. In this focused research review, we report MCP-counter, a methodology based on transcriptomic markers that assesses the proportion of several immune and stromal cell populations in the TME from transcriptomic data, and we highlight how it can provide a way to decipher the complex mechanisms at play in tumors. In several malignancies, MCP-counter scores have been used to show various prognostic impacts of the TME, which we also show to be linked with the mutational burden of tumors. We also compared established molecular classifications of colorectal cancer and clear-cell renal cell carcinoma with the output of MCP-counter, and show that molecular subgroups have different TME profiles, and that these profiles are consistent within a given subgroup. Finally, we provide insights as to how knowing the TME composition may shape patient care in the near future.

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Abbreviations

ccRCC:

Clear-cell renal cell carcinoma

CIBERSORT:

Cell-type identification by estimating relative subsets of RNA transcripts

CMS:

Consensus molecular subgroups

CRC:

Colorectal cancer

GSEA:

Gene set enrichment analysis

MCP-counter:

Microenvironment cell population-counter

MSI:

Microsatellite instable

NGS:

Next-generation sequencing

NIBIT:

Network Italiano per la Bioterapia dei Tumori (the Italian network for cancer biotherapy)

TCGA PANCAN:

The cancer genome atlas pan-cancer cohort

Th17:

T helper lymphocyte producing interleukin 17

TME:

Tumor microenvironment

Treg:

Regulatory T cell

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Acknowledgements

We wish to thank Benoît Beuselinck, Laetitia Lacroix, Pierre Laurent-Puig, Stéphane Oudard, Jessica Zucman-Rossi, and all other members of the teams who contributed to the data.

Author information

Author notes

  1. Florent Petitprez and Yann A. Vano contributed equally.

Authors and Affiliations

  1. INSERM, UMR_S 1138, Cordeliers Research Center, Team Cancer, Immune Control and Escape, 75006, Paris, France

    Florent Petitprez, Yann A. Vano, Etienne Becht, Nicolas A. Giraldo, Catherine Sautès-Fridman & Wolf H. Fridman

  2. University Paris Descartes Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, Eq. 13 escalier E 3e étage, 15 rue de l’école de médecine, 75006, Paris, France

    Florent Petitprez, Yann A. Vano, Etienne Becht, Nicolas A. Giraldo, Catherine Sautès-Fridman & Wolf H. Fridman

  3. University UPMC Paris 6, Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, 75006, Paris, France

    Florent Petitprez, Yann A. Vano, Etienne Becht, Nicolas A. Giraldo, Catherine Sautès-Fridman & Wolf H. Fridman

  4. Programme Cartes d’Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France

    Florent Petitprez & Aurélien de Reyniès

  5. Department of Medical Oncology, Georges Pompidou European Hospital, University Paris Descartes Paris 5, Paris, France

    Yann A. Vano

  6. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore

    Etienne Becht

Authors
  1. Florent Petitprez
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Corresponding author

Correspondence to Wolf H. Fridman.

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Funding

This work was supported by the Institut National de la santé et de la Recherche Medicale (INSERM), University Paris-Descartes, University Pierre and Marie Curie, the Site de Recherche Integrée sur le Cancer (SIRIC) Cancer Research for Personalized Medicine (CARPEM) program, the LabEx Immuno-Oncology (LAXE62_9UMRS972 FRIDMAN), the Institut National Du Cancer (INCa), and the Cancéropôle Ile-de-France, O. Lecomte. Florent Petitprez is recipient of a CARPEM fellowship.

Conflict of interest

Yann A. Vano has received speaker honoraria from Novartis, Pfizer, Bristol-Myers-Squibb, and Astellas Sanofi, and has received financial support for attending symposia from Bristol-Myers-Squibb and Novartis. Aurélien de Reyniès holds intellectual property rights for patents related to immune cell population abundance estimation through transcriptomic analysis. Wolf H. Fridman is a consultant for Pierre Fabre Medicament, Sanofi, Bristol-Myers-Squibb, Novartis, Curetech, Servier, Efranet, Efralys, and Adaptimmune. All other authors declare no conflicts of interest.

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Petitprez, F., Vano, Y.A., Becht, E. et al. Transcriptomic analysis of the tumor microenvironment to guide prognosis and immunotherapies. Cancer Immunol Immunother 67, 981–988 (2018). https://doi.org/10.1007/s00262-017-2058-z

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  • DOI: https://doi.org/10.1007/s00262-017-2058-z

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