The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis

Mlecnik B, Bindea G, Kirilovsky A, Angell HK, Obenauf AC, Tosolini M, Church SE, Maby P, Vasaturo A, Angelova M, Fredriksen T, Mauger S, Waldner M, Berger A, Speicher MR, Pages F, Valge-Archer V, Galon J (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Science Translational Medicine American Association for the Advancement of Science

Book Volume: 8

Pages Range: 327ra26

Journal Issue: 327

DOI: 10.1126/scitranslmed.aad6352

Abstract

Although distant metastases account for most of the deaths in cancer patients, fundamental questions regarding mechanisms that promote or inhibit metastasis remain unanswered. We show the impact of mutations, genomic instability, lymphatic and blood vascularization, and the immune contexture of the tumor microenvironment on synchronous metastases in large cohorts of colorectal cancer patients. We observed large genetic heterogeneity among primary tumors, but no major differences in chromosomal instability or key cancer-associated mutations. Similar patterns of cancer-related gene expression levels were observed between patients. No cancer-associated genes or pathways were associated with M stage. Instead, mutations of FBXW7 were associated with the absence of metastasis and correlated with increased expression of T cell proliferation and antigen presentation functions. Analyzing the tumor microenvironment, we observed two hallmarks of the metastatic process: decreased presence of lymphatic vessels and reduced immune cytotoxicity. These events could be the initiating factors driving both synchronous and metachronous metastases. Our data demonstrate the protective impact of the Immunoscore, a cytotoxic immune signature, and increased marginal lymphatic vessels, against the generation of distant metastases, regardless of genomic instability.

Authors with CRIS profile

Maximilian Waldner Professur für Funktionelle Bildgebung in der Medizin

Involved external institutions

National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Georges Pompidou European Hospital / Hôpital Européen Georges-Pompidou (HEGP) FR France (FR) MedImmune LLC US United States (USA) (US)

How to cite

APA:

Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, H.K., Obenauf, A.C., Tosolini, M.,... Galon, J. (2016). The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Science Translational Medicine, 8(327), 327ra26. https://doi.org/10.1126/scitranslmed.aad6352

MLA:

Mlecnik, Bernhard, et al. "The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis." Science Translational Medicine 8.327 (2016): 327ra26.

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