Research status of role of cancer-associated fibroblasts in regulation of immune response in tumor microenvironment_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LING Yuwei ,  KANG Hua

Center for Thyroid and Breast Surgery, Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P. R. China;

Corresponding author：

KANG Hua, Email: kanghua@xwh.ccmu.edu.cn

Keywords：

cancer-associated fibroblasts; immunoregualtion; tumor microenvironment

DOI：

10.7507/1007-9424.202003104

Video：

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Objective To introduce the research status of the immunoregulation function of cancer-associated fibroblasts (CAFs) in tumor microenvironment.Method The literatures in recent years on the studies of role of CAFs in the regulation of immune response in the tumor microenvironment were collected and summarized.Results The CAFs played a critical role as the components of the tumor microenvironment. The CAFs could product various growth factors and cytokines that were contributed to the immunoregulation including the polarization of the immune cells and the regulation of the function of immune cells in the tumor microenvironment and eventually resulted in the carcinogenesis, tumor progression, invasion, metastasis and therapy resistance.Conclusion CAFs play a significant role in the immunoregulation in tumor microenvironment, but as a potential target for breast cancer, more studies are still needed to discover the specific markers, heterogeneity, and key signaling pathways.

Citation： LING Yuwei, KANG Hua. Research status of role of cancer-associated fibroblasts in regulation of immune response in tumor microenvironment. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(12): 1593-1597. doi: 10.7507/1007-9424.202003104 Copy

1.	Buchsbaum RJ, Oh SY. Breast cancer-associated fibroblasts: where we are and where we need to go. Cancers (Basel), 2016, 8(2): 19.
2.	Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer, 2020, 20(3): 174-186.
3.	Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer, 2006, 6(5): 392-401.
4.	Tomasek JJ, Gabbiani G, Hinz B, et al. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol, 2002, 3(5): 349-363.
5.	Cui Q, Wang B, Li K, et al. Upregulating MMP-1 in carcinoma-associated fibroblasts reduces the efficacy of taxotere on breast cancer synergized by collagen Ⅳ. Oncol Lett, 2018, 16(3): 3537-3544.
6.	Wang B, Xi C, Liu M, et al. Breast fibroblasts in both cancer and normal tissues induce phenotypic transformation of breast cancer stem cells: a preliminary study. Peer J, 2018, 6: e4805.
7.	Chen Z, Yan X, Li K, et al. Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling. Clin Transl Oncol, 2020, 22(4): 522-531.
8.	Luo H, Tu G, Liu Z, et al. Cancer-associated fibroblasts: a multifaceted driver of breast cancer progression. Cancer Lett, 2015, 361(2): 155-163.
9.	王碧霄, 席春芳, 康骅. 肿瘤相关成纤维细胞对乳腺癌干细胞的影响及机制研究进展. 中国普外基础与临床杂志, 2018, 25(1): 108-112.
10.	Mao Y, Keller ET, Garfield DH, et al. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev, 2013, 32(1-2): 303-315.
11.	Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell, 2018, 33(3): 463-479.
12.	Rønnov-Jessen L, Petersen OW, Koteliansky VE, et al. The origin of the myofibroblasts in breast cancercancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. J Clin Invest, 1995, 95(2): 859-873.
13.	Kojima Y, Acar A, Eaton EN, et al. Autocrine TGF-beta and stromal cell-derived factor-1(SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci USA, 2010, 107(46): 20009-20014.
14.	Mishra PJ, Mishra PJ, Humeniuk R, et al. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res, 2008, 68(11): 4331-4339.
15.	Weber CE, Kothari AN, Wai PY, et al. Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene, 2015, 34(37): 4821-4833.
16.	Jotzu C, Alt E, Welte G, et al. Adipose tissue-derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor-derived factors. Anal Cell Pathol (Amst), 2010, 33(2): 61-79.
17.	Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res, 2009, 15(2): 425-430.
18.	Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell, 2010, 140(6): 883-899.
19.	Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev, 2008, 224: 141-165.
20.	Fearon DT. The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunol Res, 2014, 2(3): 187-193.
21.	Tjomsland V, Spångeus A, Välilä J, et al. Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts. Neoplasia, 2011, 13(8): 664-675.
22.	Chen L, Wang S, Wang Y, et al. IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor. Oncotarget, 2018, 9(25): 17443-17454.
23.	Donzelli S, Milano E, Pruszko M, et al. Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages. Breast Cancer Res, 2018, 20(1): 59.
24.	Albini A, Bruno A, Noonan DM, et al. Contribution to tumor angiogenesis from innate immune cells within the tumor microenvironment: implications for immunotherapy. Front Immunol, 2018, 9: 527.
25.	Gok Yavuz B, Gunaydin G, Gedik ME, et al. Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1⁺ TAMs. Sci Rep, 2019, 9(1): 3172.
26.	Acharyya S, Oskarsson T, Vanharanta S, et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell, 2012, 150(1): 165-178.
27.	Pereira BA, Lister NL, Hashimoto K, et al. Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro. Biomaterials, 2019, 197: 72-85.
28.	Cheng Y, Li H, Deng Y, et al. Cancer-associated fibroblasts induce PDL1⁺ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma. Cell Death Dis, 2018, 9(4): 422.
29.	Zhang R, Qi F, Zhao F, et al. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis, 2019, 10(4): 273.
30.	Laouar Y, Sutterwala FS, Gorelik L, et al. Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat Immunol, 2005, 6(6): 600-607.
31.	Ziani L, Safta-Saadoun TB, Gourbeix J, et al. Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion. Oncotarget, 2017, 8(12): 19780-19794.
32.	De Monte L, Reni M, Tassi E, et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med, 2011, 208(3): 469-478.
33.	Liao D, Luo Y, Markowitz D, et al. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One, 2009, 4(11): e7965.
34.	Weber F, Byrne SN, Le S, et al. Transforming growth factor-beta1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system. Cancer Immunol Immunother, 2005, 54(9): 898-906.
35.	Larmonier N, Marron M, Zeng Y, et al. Tumor-derived CD4⁺CD25⁺ regulatory T cell suppression of dendritic cell function involves TGF-beta and IL-10. Cancer Immunol Immunother, 2007, 56(1): 48-59.
36.	Elyada E, Bolisetty M, Laise P, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov, 2019, 9(8): 1102-1123.
37.	Lakins MA, Ghorani E, Munir H, et al. Cancer-associated fibroblasts induce antigen-specific deletion of CD8⁺ T Cells to protect tumour cells. Nat Commun, 2018, 9(1): 948.
38.	Kato T, Noma K, Ohara T, et al. Cancer-associated fibroblasts affect intratumoral CD8⁺ and FoxP3⁺ T cells via IL6 in the tumor microenvironment. Clin Cancer Res, 2018, 24(19): 4820-4833.
39.	Shafer-Weaver KA, Anderson MJ, Stagliano K, et al. Cutting edge: tumor-specific CD8⁺ T cells infiltrating prostatic tumors are induced to become suppressor cells. J Immunol, 2009, 183(8): 4848-4852.
40.	Han Y, Guo Q, Zhang M, et al. CD69⁺CD4⁺CD25^-T cells, a new subset of regulatory T cells, suppress T cell proliferation through membrane-bound TGF-beta1. J Immunol, 2009, 182(1): 111-120.
41.	Sanjabi S, Mosaheb MM, Flavell RA. Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8⁺ T cells. Immunity, 2009, 31(1): 131-144.
42.	Thomas DA, Massagué J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell, 2005, 8(5): 369-380.
43.	Ahmadzadeh M, Rosenberg SA. TGF-beta1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol, 2005, 174(9): 5215-5223.
44.	Liu Y, Lv J, Liang X, et al. Fibrin stiffness mediates dormancy of tumor-repopulating cells via a Cdc42-driven Tet2 epigenetic program. Cancer Res, 2018, 78(14): 3926-3937.
45.	Alonso-Nocelo M, Raimondo TM, Vining KH, et al. Matrix stiffness and tumor-associated macrophages modulate epithelial to mesenchymal transition of human adenocarcinoma cells. Biofabrication, 2018, 10(3): 035004.
46.	Chen IX, Chauhan VP, Posada J, et al. Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer. Proc Natl Acad Sci USA, 2019, 116(10): 4558-4566.
47.	Kobayashi N, Miyoshi S, Mikami T, et al. Hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor neovascularization. Cancer Res, 2010, 70(18): 7073-7083.
48.	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. Cancer Cell, 2017, 32(5): 654-668.
49.	Palazón A, Aragonés J, Morales-Kastresana A, et al. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res, 2012, 18(5): 1207-1213.
50.	Ohm JE, Gabrilovich DI, Sempowski GD, et al. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood, 2003, 101(12): 4878-4886.
51.	Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 2005, 121(3): 335-348.
52.	Falcon BL, Pietras K, Chou J, et al. Increased vascular delivery and efficacy of chemotherapy after inhibition of platelet-derived growth factor-B. Am J Pathol, 2011, 178(6): 2920-2930.
53.	Liu H, Shen J, Lu K. IL-6 and PD-L1 blockade combination inhibits hepatocellular carcinoma cancer development in mouse model. Biochem Biophys Res Commun, 2017, 486(2): 239-244.
54.	Fang J, Xiao L, Joo KI, et al. A potent immunotoxin targeting fibroblast activation protein for treatment of breast cancer in mice. Int J Cancer, 2016, 138(4): 1013-1023.

1. Buchsbaum RJ, Oh SY. Breast cancer-associated fibroblasts: where we are and where we need to go. Cancers (Basel), 2016, 8(2): 19.
2. Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer, 2020, 20(3): 174-186.
3. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer, 2006, 6(5): 392-401.
4. Tomasek JJ, Gabbiani G, Hinz B, et al. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol, 2002, 3(5): 349-363.
5. Cui Q, Wang B, Li K, et al. Upregulating MMP-1 in carcinoma-associated fibroblasts reduces the efficacy of taxotere on breast cancer synergized by collagen Ⅳ. Oncol Lett, 2018, 16(3): 3537-3544.
6. Wang B, Xi C, Liu M, et al. Breast fibroblasts in both cancer and normal tissues induce phenotypic transformation of breast cancer stem cells: a preliminary study. Peer J, 2018, 6: e4805.
7. Chen Z, Yan X, Li K, et al. Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling. Clin Transl Oncol, 2020, 22(4): 522-531.
8. Luo H, Tu G, Liu Z, et al. Cancer-associated fibroblasts: a multifaceted driver of breast cancer progression. Cancer Lett, 2015, 361(2): 155-163.
9. 王碧霄, 席春芳, 康骅. 肿瘤相关成纤维细胞对乳腺癌干细胞的影响及机制研究进展. 中国普外基础与临床杂志, 2018, 25(1): 108-112.
10. Mao Y, Keller ET, Garfield DH, et al. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev, 2013, 32(1-2): 303-315.
11. Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell, 2018, 33(3): 463-479.
12. Rønnov-Jessen L, Petersen OW, Koteliansky VE, et al. The origin of the myofibroblasts in breast cancercancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. J Clin Invest, 1995, 95(2): 859-873.
13. Kojima Y, Acar A, Eaton EN, et al. Autocrine TGF-beta and stromal cell-derived factor-1(SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci USA, 2010, 107(46): 20009-20014.
14. Mishra PJ, Mishra PJ, Humeniuk R, et al. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res, 2008, 68(11): 4331-4339.
15. Weber CE, Kothari AN, Wai PY, et al. Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene, 2015, 34(37): 4821-4833.
16. Jotzu C, Alt E, Welte G, et al. Adipose tissue-derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor-derived factors. Anal Cell Pathol (Amst), 2010, 33(2): 61-79.
17. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res, 2009, 15(2): 425-430.
18. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell, 2010, 140(6): 883-899.
19. Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev, 2008, 224: 141-165.
20. Fearon DT. The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunol Res, 2014, 2(3): 187-193.
21. Tjomsland V, Spångeus A, Välilä J, et al. Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts. Neoplasia, 2011, 13(8): 664-675.
22. Chen L, Wang S, Wang Y, et al. IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor. Oncotarget, 2018, 9(25): 17443-17454.
23. Donzelli S, Milano E, Pruszko M, et al. Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages. Breast Cancer Res, 2018, 20(1): 59.
24. Albini A, Bruno A, Noonan DM, et al. Contribution to tumor angiogenesis from innate immune cells within the tumor microenvironment: implications for immunotherapy. Front Immunol, 2018, 9: 527.
25. Gok Yavuz B, Gunaydin G, Gedik ME, et al. Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1⁺ TAMs. Sci Rep, 2019, 9(1): 3172.
26. Acharyya S, Oskarsson T, Vanharanta S, et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell, 2012, 150(1): 165-178.
27. Pereira BA, Lister NL, Hashimoto K, et al. Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro. Biomaterials, 2019, 197: 72-85.
28. Cheng Y, Li H, Deng Y, et al. Cancer-associated fibroblasts induce PDL1⁺ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma. Cell Death Dis, 2018, 9(4): 422.
29. Zhang R, Qi F, Zhao F, et al. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis, 2019, 10(4): 273.
30. Laouar Y, Sutterwala FS, Gorelik L, et al. Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat Immunol, 2005, 6(6): 600-607.
31. Ziani L, Safta-Saadoun TB, Gourbeix J, et al. Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion. Oncotarget, 2017, 8(12): 19780-19794.
32. De Monte L, Reni M, Tassi E, et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med, 2011, 208(3): 469-478.
33. Liao D, Luo Y, Markowitz D, et al. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One, 2009, 4(11): e7965.
34. Weber F, Byrne SN, Le S, et al. Transforming growth factor-beta1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system. Cancer Immunol Immunother, 2005, 54(9): 898-906.
35. Larmonier N, Marron M, Zeng Y, et al. Tumor-derived CD4⁺CD25⁺ regulatory T cell suppression of dendritic cell function involves TGF-beta and IL-10. Cancer Immunol Immunother, 2007, 56(1): 48-59.
36. Elyada E, Bolisetty M, Laise P, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov, 2019, 9(8): 1102-1123.
37. Lakins MA, Ghorani E, Munir H, et al. Cancer-associated fibroblasts induce antigen-specific deletion of CD8⁺ T Cells to protect tumour cells. Nat Commun, 2018, 9(1): 948.
38. Kato T, Noma K, Ohara T, et al. Cancer-associated fibroblasts affect intratumoral CD8⁺ and FoxP3⁺ T cells via IL6 in the tumor microenvironment. Clin Cancer Res, 2018, 24(19): 4820-4833.
39. Shafer-Weaver KA, Anderson MJ, Stagliano K, et al. Cutting edge: tumor-specific CD8⁺ T cells infiltrating prostatic tumors are induced to become suppressor cells. J Immunol, 2009, 183(8): 4848-4852.
40. Han Y, Guo Q, Zhang M, et al. CD69⁺CD4⁺CD25^-T cells, a new subset of regulatory T cells, suppress T cell proliferation through membrane-bound TGF-beta1. J Immunol, 2009, 182(1): 111-120.
41. Sanjabi S, Mosaheb MM, Flavell RA. Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8⁺ T cells. Immunity, 2009, 31(1): 131-144.
42. Thomas DA, Massagué J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell, 2005, 8(5): 369-380.
43. Ahmadzadeh M, Rosenberg SA. TGF-beta1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol, 2005, 174(9): 5215-5223.
44. Liu Y, Lv J, Liang X, et al. Fibrin stiffness mediates dormancy of tumor-repopulating cells via a Cdc42-driven Tet2 epigenetic program. Cancer Res, 2018, 78(14): 3926-3937.
45. Alonso-Nocelo M, Raimondo TM, Vining KH, et al. Matrix stiffness and tumor-associated macrophages modulate epithelial to mesenchymal transition of human adenocarcinoma cells. Biofabrication, 2018, 10(3): 035004.
46. Chen IX, Chauhan VP, Posada J, et al. Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer. Proc Natl Acad Sci USA, 2019, 116(10): 4558-4566.
47. Kobayashi N, Miyoshi S, Mikami T, et al. Hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor neovascularization. Cancer Res, 2010, 70(18): 7073-7083.
48. 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. Cancer Cell, 2017, 32(5): 654-668.
49. Palazón A, Aragonés J, Morales-Kastresana A, et al. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res, 2012, 18(5): 1207-1213.
50. Ohm JE, Gabrilovich DI, Sempowski GD, et al. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood, 2003, 101(12): 4878-4886.
51. Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 2005, 121(3): 335-348.
52. Falcon BL, Pietras K, Chou J, et al. Increased vascular delivery and efficacy of chemotherapy after inhibition of platelet-derived growth factor-B. Am J Pathol, 2011, 178(6): 2920-2930.
53. Liu H, Shen J, Lu K. IL-6 and PD-L1 blockade combination inhibits hepatocellular carcinoma cancer development in mouse model. Biochem Biophys Res Commun, 2017, 486(2): 239-244.
54. Fang J, Xiao L, Joo KI, et al. A potent immunotoxin targeting fibroblast activation protein for treatment of breast cancer in mice. Int J Cancer, 2016, 138(4): 1013-1023.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research status of role of cancer-associated fibroblasts in regulation of immune response in tumor microenvironment

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