RT Journal Article
SR Electronic
T1 Functional Network Pipeline Reveals Genetic Determinants Associated with in Situ Lymphocyte Proliferation and Survival of Cancer Patients
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 228ra37
OP 228ra37
DO 10.1126/scitranslmed.3007240
VO 6
IS 228
A1 Mlecnik, Bernhard
A1 Bindea, Gabriela
A1 Angell, Helen K.
A1 Sasso, Maria Stella
A1 Obenauf, Anna C.
A1 Fredriksen, Tessa
A1 Lafontaine, Lucie
A1 Bilocq, Amelie M.
A1 Kirilovsky, Amos
A1 Tosolini, Marie
A1 Waldner, Maximilian
A1 Berger, Anne
A1 Fridman, Wolf Herman
A1 Rafii, Arash
A1 Valge-Archer, Viia
A1 Pagès, Franck
A1 Speicher, Michael R.
A1 Galon, Jérôme
YR 2014
UL http://stm.sciencemag.org/content/6/228/228ra37.abstract
AB 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.