Macrophages in human colorectal cancer are pro-inflammatory and prime T cells towards an anti-tumour type-1 inflammatory response

被引:117
作者
Ong, Siew-Min [1 ]
Tan, Yann-Chong [1 ]
Beretta, Ottavio [1 ]
Jiang, Dongsheng [2 ,3 ]
Yeap, Wei-Hseun [1 ]
Tai, June J. Y. [1 ]
Wong, Wing-Cheong [4 ]
Yang, Henry [1 ]
Schwarz, Herbert [2 ,3 ]
Lim, Kiat-Hon [5 ]
Koh, Poh-Koon [6 ]
Ling, Khoon-Lin [7 ]
Wong, Siew-Cheng [1 ]
机构
[1] Singapore Immunol Network, Singapore, Singapore
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore
[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Program Immunol, Singapore 117595, Singapore
[4] Bioinformat Inst BII, Singapore, Singapore
[5] Singapore Gen Hosp, Dept Pathol, Singapore 0316, Singapore
[6] Singapore Gen Hosp, Dept Colorectal Surg, Singapore 0316, Singapore
[7] Singapore Gen Hosp, Dept Gastroenterol, Singapore 0316, Singapore
关键词
Chemokines; Cytokines; Spheroid model; T-cell co-stimulation; Tumour-associated macrophages (TAMs); TUMOR-ASSOCIATED MACROPHAGES; INTERFERON-GAMMA; PROGRESSION; POLARIZATION; INFILTRATION; PLASTICITY; DENSITY; TARGETS; GROWTH; TM4;
D O I
10.1002/eji.201141825
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
High macrophage infiltration into tumours often correlates with poor prognoses; in colorectal, stomach and skin cancers, however, the opposite is observed but the mechanisms behind this phenomenon remain unclear. Here, we sought to understand how tumour-associated macrophages (TAMs) in colorectal cancer execute tumour-suppressive roles. We found that TAMs in a colorectal cancer model were pro-inflammatory and inhibited the proliferation of tumour cells. TAMs also produced chemokines that attract T cells, stimulated proliferation of allogeneic T cells and activated type-1 T cells associated with anti-tumour immune responses. Using colorectal tumour tissues, we verified that TAMs in vivo were indeed pro-inflammatory. Furthermore, the number of tumour-infiltrating T cells correlated with the number of TAMs, suggesting that TAMs could attract T cells; and indeed, type-1 T cells were present in the tumour tissues. Patient clinical data suggested that TAMs exerted tumour-suppressive effects with the help of T cells. Hence, the tumour-suppressive mechanisms of TAMs in colorectal cancer involve the inhibition of tumour cell proliferation alongside the production of pro-inflammatory cytokines, chemokines and promoting type-1 T-cell responses. These new findings would contribute to the development of future cancer immunotherapies based on enhancing the tumour-suppressive properties of TAMs to boost anti-tumour immune responses.
引用
收藏
页码:89 / 100
页数:12
相关论文
共 35 条
[1]   Interferon-alpha, -beta and -gamma induce CXCL9 and CXCL10 secretion by human thyrocytes: Modulation by peroxisome proliferator-activated receptor-gamma agonists [J].
Antonelli, Alessandro ;
Ferrari, Silvia Martina ;
Fallahi, Poupak ;
Ghiri, Emiliano ;
Crescioli, Clara ;
Romagnani, Paola ;
Vitti, Paolo ;
Serio, Mario ;
Ferrannini, Ele .
CYTOKINE, 2010, 50 (03) :260-267
[2]   The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies [J].
Bingle, L ;
Brown, NJ ;
Lewis, CE .
JOURNAL OF PATHOLOGY, 2002, 196 (03) :254-265
[3]   Plasticity of macrophage function during tumor progression: Regulation by distinct molecular mechanisms [J].
Biswas, Subhra K. ;
Sica, Antonio ;
Lewis, Claire E. .
JOURNAL OF IMMUNOLOGY, 2008, 180 (04) :2011-2017
[4]   Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm [J].
Biswas, Subhra K. ;
Mantovani, Alberto .
NATURE IMMUNOLOGY, 2010, 11 (10) :889-896
[5]   Production of interferon-γ by myeloid cells -: fact or fancy? [J].
Bogdan, Christian ;
Schleicher, Ulrike .
TRENDS IN IMMUNOLOGY, 2006, 27 (06) :282-290
[6]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193
[7]   Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence [J].
Camus, Matthieu ;
Tosolini, Marie ;
Mlecnik, Bernhard ;
Pages, Franck ;
Kirilovsky, Amos ;
Berger, Anne ;
Costes, Anne ;
Bindea, Gabriela ;
Charoentong, Pornpimol ;
Bruneval, Patrick ;
Trajanoski, Zlatko ;
Fridman, Wolf-Herman ;
Galon, Jerome .
CANCER RESEARCH, 2009, 69 (06) :2685-2693
[8]   Primary antitumor immune response mediated by CD4+ T cells [J].
Corthay, A ;
Skovseth, DK ;
Lundin, KU ;
Rosjo, E ;
Omholt, H ;
Hofgaard, PO ;
Haraldsen, G ;
Bogen, B .
IMMUNITY, 2005, 22 (03) :371-383
[9]   Interferon-γ reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages [J].
Duluc, Dorothee ;
Corvaisier, Murielle ;
Blanchard, Simon ;
Catala, Laurent ;
Descamps, Philippe ;
Gamelin, Erick ;
Ponsoda, Stephane ;
Delneste, Yves ;
Hebbar, Mohamed ;
Jeannin, Pascale .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (02) :367-373
[10]   Cancer immunoediting: from immunosurveillance to tumor escape [J].
Dunn, GP ;
Bruce, AT ;
Ikeda, H ;
Old, LJ ;
Schreiber, RD .
NATURE IMMUNOLOGY, 2002, 3 (11) :991-998