Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients
Mlecnik B, Bindea G, Angell HK, Sasso MS, Obenauf AC, Fredriksen T, Lafontaine L, Bilocq AM, Kirilovsky A, Tosolini M, Waldner M, Berger A, Fridman WH, Rafii A, Valge-Archer V, Pages F, Speicher MR, Galon J (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Book Volume: 6
Pages Range: 228ra37
Journal Issue: 228
DOI: 10.1126/scitranslmed.3007240
Abstract
The tumor microenvironment is host to a complex network of cytokines that contribute to shaping the intratumoral immune reaction. Chromosomal gains and losses, coupled with expression analysis, of 59 cytokines and receptors and their functional networks were investigated in colorectal cancers. Changes in local expression for 13 cytokines were shown. Metastatic patients exhibited an increased frequency of deletions of cytokines from chromosome 4. Interleukin 15 (IL15) deletion corresponded with decreased IL15 expression, a higher risk of tumor recurrence, and reduced patient survival. Decreased IL15 expression affected the local proliferation of B and T lymphocytes. Patients with proliferating B and T cells at the invasive margin and within the tumor center had significantly prolonged disease-free survival. These results delineate chromosomal instability as a mechanism of modulating local cytokine expression in human tumors and underline the major role of IL15. Our data provide further mechanisms resulting in changes of specific immune cell densities within the tumor, and the importance of local active lymphocyte proliferation for patient survival.
Authors with CRIS profile
Involved external institutions
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
France (FR)
AstraZeneca UK Limited
United Kingdom (GB)
Weill Cornell Medicine-Qatar (WCM-Q)
Qatar (QA)
University of Paris 5 - René Descartes / Université Paris V René Descartes
France (FR)
Assistance Publique-Hôpitaux de Paris (AP-HP)
France (FR)
France (FR)
AstraZeneca UK Limited
United Kingdom (GB)
Weill Cornell Medicine-Qatar (WCM-Q)
Qatar (QA)
University of Paris 5 - René Descartes / Université Paris V René Descartes
France (FR)
Assistance Publique-Hôpitaux de Paris (AP-HP)
France (FR)
How to cite
APA:
Mlecnik, B., Bindea, G., Angell, H.K., Sasso, M.S., Obenauf, A.C., Fredriksen, T.,... Galon, J. (2014). Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients. Science Translational Medicine, 6(228), 228ra37. https://dx.doi.org/10.1126/scitranslmed.3007240
MLA:
Mlecnik, Bernhard, et al. "Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients." Science Translational Medicine 6.228 (2014): 228ra37.
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