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@article{Roumenina:2019:10.1158/2326-6066.CIR-18-0891,
author = {Roumenina, LT and Daugan, MV and Noé, R and Petitprez, F and Vano, YA and Sanchez-Salas, R and Becht, E and Meilleroux, J and Clec'h, BL and Giraldo, NA and Merle, NS and Sun, C-M and Verkarre, V and Validire, P and Selves, J and Lacroix, L and Delfour, O and Vandenberghe, I and Thuilliez, C and Keddani, S and Sakhi, IB and Barret, E and Ferré, P and Corvaïa, N and Passioukov, A and Chetaille, E and Botto, M and de, Reynies A and Oudard, SM and Mejean, A and Cathelineau, X and Sautès-Fridman, C and Fridman, WH},
doi = {10.1158/2326-6066.CIR-18-0891},
journal = {Cancer Immunology Research},
pages = {1091--1105},
title = {Tumor cells hijack macrophage-produced complement C1q to promote tumor growth},
url = {http://dx.doi.org/10.1158/2326-6066.CIR-18-0891},
volume = {7},
year = {2019}
}

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TY  - JOUR
AB  - Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of complement component 5a (C5a). However, the activation pathways that generate C5a in tumors remain obscure. By data mining, we identified ccRCC as a cancer type expressing concomitantly high expression of the components that are part of the classical complement pathway. To understand how the complement cascade is activated in ccRCC and impacts patients' clinical outcome, primary tumors from three patient cohorts (n = 106, 154, and 43), ccRCC cell lines, and tumor models in complement-deficient mice were used. High densities of cells producing classical complement pathway components C1q and C4 and the presence of C4 activation fragment deposits in primary tumors correlated with poor prognosis. The in situ orchestrated production of C1q by tumor-associated macrophages (TAM) and C1r, C1s, C4, and C3 by tumor cells associated with IgG deposits, led to C1 complex assembly, and complement activation. Accordingly, mice deficient in C1q, C4, or C3 displayed decreased tumor growth. However, the ccRCC tumors infiltrated with high densities of C1q-producing TAMs exhibited an immunosuppressed microenvironment, characterized by high expression of immune checkpoints (i.e., PD-1, Lag-3, PD-L1, and PD-L2). Our data have identified the classical complement pathway as a key inflammatory mechanism activated by the cooperation between tumor cells and TAMs, favoring cancer progression, and highlight potential therapeutic targets to restore an efficient immune reaction to cancer.
AU  - Roumenina,LT
AU  - Daugan,MV
AU  - Noé,R
AU  - Petitprez,F
AU  - Vano,YA
AU  - Sanchez-Salas,R
AU  - Becht,E
AU  - Meilleroux,J
AU  - Clec'h,BL
AU  - Giraldo,NA
AU  - Merle,NS
AU  - Sun,C-M
AU  - Verkarre,V
AU  - Validire,P
AU  - Selves,J
AU  - Lacroix,L
AU  - Delfour,O
AU  - Vandenberghe,I
AU  - Thuilliez,C
AU  - Keddani,S
AU  - Sakhi,IB
AU  - Barret,E
AU  - Ferré,P
AU  - Corvaïa,N
AU  - Passioukov,A
AU  - Chetaille,E
AU  - Botto,M
AU  - de,Reynies A
AU  - Oudard,SM
AU  - Mejean,A
AU  - Cathelineau,X
AU  - Sautès-Fridman,C
AU  - Fridman,WH
DO  - 10.1158/2326-6066.CIR-18-0891
EP  - 1105
PY  - 2019///
SN  - 2326-6066
SP  - 1091
TI  - Tumor cells hijack macrophage-produced complement C1q to promote tumor growth
T2  - Cancer Immunology Research
UR  - http://dx.doi.org/10.1158/2326-6066.CIR-18-0891
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31164356
UR  - http://hdl.handle.net/10044/1/70575
VL  - 7
ER  -

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