肿瘤免疫治疗不容忽视的微环境:癌相关成纤维细胞
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摘要
癌相关成纤维细胞(cancer associated fibroblasts,CAF),肿瘤微环境中宿主细胞主要成分,除具有直接促瘤作用外,还可通过抑制T细胞功能、促进免疫抑制细胞功能、调节胞外基质结构参与肿瘤免疫抑制微环境的形成。抑制CAF功能和以CAF为靶点的抗肿瘤微环境治疗为免疫治疗提供新的辅助手段。
Cancer associated fibroblasts(CAF),the main components of the host cells in the tumor microenvironment,not only have a direct "tumor promoting" role,but also participate in the formation of immunosuppressive microenvironment by inhibiting T lymphocyte function,promoting immunosuppressive cell function,and regulating the structure of extracellular matrix. Anti-tumor microenvironment therapy that inhibits CAF function would provide a new auxiliary method for immunotherapy.
Cancer associated fibroblasts(CAF),the main components of the host cells in the tumor microenvironment,not only have a direct "tumor promoting" role,but also participate in the formation of immunosuppressive microenvironment by inhibiting T lymphocyte function,promoting immunosuppressive cell function,and regulating the structure of extracellular matrix. Anti-tumor microenvironment therapy that inhibits CAF function would provide a new auxiliary method for immunotherapy.
引文
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[35]Meng M,Wang W,Yan J,et al.Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model[J].Tumour Biol,2016,37(8):10317-10327.
[36]Duperret EK,Trautz A,Ammons D,et al.Alteration of the tumor stroma using a consensus DNA vaccine targeting fibroblast activation protein(FAP)synergizes with antitumor vaccine therapy in mice[J].Clin Cancer Res,2018,24(5):1190-1201.
[37]Zhen Z,Tang W,Wang M,et al.Protein nanocage mediated fibroblast-activation protein targeted photoimmunotherapy to enhance cytotoxic T cell infiltration and tumor control[J].Nano Lett,2017,17(2):862-869.
[2]Nair N,Calle AS,Zahra MH,et al.A cancer stem cell model as the point of origin of cancerassociated fibroblasts in tumor microenvironment[J].Sci Rep,2017,7(1):6838.
[3]Lei S,Ti X,Krause U,et al.Inhibition of TGF-beta/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects[J].Stem Cells,2012,30(12):2810-2819.
[4]Lin F,Wang N,Zhang T.The role of endothelial-mesenchymal transition in development and pathological process[J].IUBMB Life,2012,64(9):717-723.
[5]Ishii G,Ochiai A,Neri S.Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment[J].Adv Drug Deliv Rev,2016,99(Pt B):186-196.
[6]Kalluri R.The biology and function of fibroblasts in cancer[J].Nat Rev Cancer,2016,16(9):582-598.
[7]Tao L,Huang G,Wang R,et al.Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway[J].Sci Rep,2016,6:38408.
[8]Ziani L,Chouaib S,Thiery J.Alteration of the antitumor immune response by cancer-associated fibroblasts[J].Front Immunol,2018,9:414.
[9]Cohen N,Shani O,Raz Y,et al.Fibroblasts drive an immunosuppressive and growth-promoting microenvironment in breast cancer via secretion of chitinase 3-like 1[J].Oncogene,2017,36(31):4457-4468.
[10]Chen L,Qiu X,Wang X,et al.FAP positive fibroblasts induce immune checkpoint blockade resistance in colorectal cancer via promoting immunosuppression[J].Biochem Biophys Res Commun,2017,487(1):8-14.
[11]Koeck S,Kern J,Zwierzina M,et al.The influence of stromal cells and tumor-microenvironment-derived cytokines and chemokines on CD3(+)CD8(+)tumor infiltrating lymphocyte subpopulations[J].Oncoimmunology,2017,6(6):e1323617.
[12]Takahashi H,Sakakura K,Chikamatsu K.Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma[J].Cancer Immunol Immunother,2015,64(11):1407-1417.
[13]Cheng YS,Li H,Deng YN,et al.Cancer-associated fibroblasts induce PDL1+neutrophils through the IL6-STAT3pathway that foster immune suppression in hepatocellular carcinoma[J].Cell Death and Disease,2018,9:422.
[14]Lakins MA,Ghorani E,Munir H,et al.Cancer-associated fibroblasts induce antigen-specific deletion of CD8+T cells to protect tumour cells[J].Nat Commun,2018,9(1):948.
[15]Hatzioannou A,Nayar S,Gaitanis A,et al.Intratumoral accumulation of podoplanin-expressing lymph node stromal cells promote tumor growth through elimination of CD4+tumor-infiltrating lymphocytes[J].Oncol Immunology,2016,5(9):e1216289.
[16]Davis RJ,Van Waes C,Allen CT.Overcoming barriers to effective immunotherapy:MDSCs,TAMs,and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer[J].Oral Oncol,2016,58:59-70.
[17]Deng Y,Cheng J,Fu B,et al.Hepatic carcinoma-associated fibroblasts enhance immune suppression by facilitating the generation of myeloid-derived suppressor cells[J]Oncogene,2017,36(8):1090-1101.
[18]Ouyang L,Chang W,Fang B,et al.Estrogen-induced SDF-1alpha production promotes the progression of ER-negative breast cancer via the accumulation of MDSCs in the tumor microenvironment[J].Sci Rep,2016,6:39541.
[19]Yang X,Lin Y,Shi Y,et al.FAP promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3-CCL2 signaling[J].Cancer Res,2016,76(14):4124-4135.
[20]Zhang H,Maric I,Diprima MJ,et al.Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer[J].Blood,2013,122(7):1105-1113.
[21]Gunaydin G,Kesikli SA,Guc D.Cancer associated fibroblasts have phenotypic and functional characteristics similar to the fibrocytes that represent a novel MDSC subset[J].Oncoimmunology,2015,4(9):e1034918.
[22]Kuen J,Darowski D,Kluge T,et al.Pancreatic cancer cell/fibroblast co-culture induces M2 like macrophages that influence therapeutic response in a 3D model[J].PLoS One,2017,12(7):e182039.
[23]Cheng J,Deng Y,Yi H,et al.Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation[J].Oncogenesis,2016,5(2):e198.
[24]Stromnes IM,Schmitt TM,Hulbert A,et al.T cells engineered against a native antigen can surmount immunologic and physical barriers to treat pancreatic ductal adenocarcinoma[J].Cancer Cell,2015,28(5):638-652.
[25]Wolf K,Te LM,Krause M,et al.Physical limits of cell migration:control by ECM space and nuclear deformation and tuning by proteolysis and traction force[J].J Cell Biol,2013,201(7):1069-1084.
[26]Miles FL,Sikes RA.Insidious changes in stromal matrix fuel cancer progression[J].Mol Cancer Res,2014,12(3):297-312.
[27]Cavaco A,Rezaei M,Niland S,et al.Collateral damage intended-cancer-associated fibroblasts and vasculature are potential targets in cancer therapy[J].Int J Mol Sci,2017,18(11):pii.E2355.
[28]Ni WD,Yang ZT,Cui CA,et al.Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer[J].Biochem Biophys Res Commun,2017,486(3):607-612.
[29]Jiang H,Hegde S,Denardo DG.Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy[J].Cancer Immunol Immunother,2017,66(8):1037-1048.
[30]Zhang K,Grither WR,Van Hove S,et al.Mechanical signals regulate and activate SNAIL1 protein to control the fibrogenic response of cancer-associated fibroblasts[J].JCell Sci,2016,129(10):1989-2002.
[31]Feig C,Jones JO,Kraman M,et al.Targeting CXCL12 from FAP-expressing carcinomaassociated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer[J].Proc Natl Acad Sci USA,2013,110(50):20212-20217.
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[33]Kumar V,Donthireddy L,Marvel D,et al.Cancer-associated fibroblasts neutralize the anti-tumor effect of csf1 receptor blockade by inducing PMN-MDSC infiltration of tumors[J].Cancer Cell,2017,32(5):654-668.
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[35]Meng M,Wang W,Yan J,et al.Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model[J].Tumour Biol,2016,37(8):10317-10327.
[36]Duperret EK,Trautz A,Ammons D,et al.Alteration of the tumor stroma using a consensus DNA vaccine targeting fibroblast activation protein(FAP)synergizes with antitumor vaccine therapy in mice[J].Clin Cancer Res,2018,24(5):1190-1201.
[37]Zhen Z,Tang W,Wang M,et al.Protein nanocage mediated fibroblast-activation protein targeted photoimmunotherapy to enhance cytotoxic T cell infiltration and tumor control[J].Nano Lett,2017,17(2):862-869.
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