Research Progress of Myeloid Derived Suppressor Cells and Pancreatic Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIUQiao-fei ,  LIAOQuan

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;

Corresponding author：

LIAOQuan, Email: lqpumc@126.com

Keywords：

Pancreatic cancer; Myeloid derived suppress cell; Tumor microenvironment; Tumor immunology; Comprehensive therapy

DOI：

10.7507/1007-9424.20140246

Video：

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Objective To review the research advances about myeloid derived suppressor cells(MDSC)and pancreatic cancer, and explore the future research trends. Method Related literatures in recent 5 years from abroad databases(PubMed, Web of Science, and EMBASE)and domestic databases(CNKI, WANFANG, and WEIPU)were collected and reviewed. Results The MDSC was the core of tumor immune regulation network in pancreatic cancer microenvironment, it formed a complicated feedback with the pancreatic cancer and the stellate cells. MDSC could promote the cancerogensis and progression of pancreatic cancer, and the accumulation of MDSC in peripheral blood of pancreatic cancer patient could predict the poor prognosis. However up to now, the literatures about the relation between MDSC and the chemotherapy and metastasis of pancreatic cancer were limited. Conclusions The comprehensive therapy by targeting MDSC of pancreatic cancer is promising. However, many issues need to be further investigated.

Citation： LIUQiao-fei, LIAOQuan. Research Progress of Myeloid Derived Suppressor Cells and Pancreatic Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(8): 1024-1028. doi: 10.7507/1007-9424.20140246 Copy

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2.	Vincent A, Herman J, Schulick R, et al. Pancreatic cancer[J]. Lancet, 2011, 378(9791):607-620.
3.	Apte MV, Wilson JS, Lugea A, et al. A starring role for stellate cells in the pancreatic cancer microenvironment[J]. Gastroenterology, 2013, 144(6):1210-1219.
4.	Talmadge JE, Gabrilovich DI. History of myeloid-derived suppressor cells[J]. Nat Rev Cancer, 2013, 13(10):739-752.
5.	Zhao F, Obermann S, von Wasielewski R, et al. Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma[J]. Immunology, 2009, 128(1): 141-149.
6.	Vernon PJ, Loux TJ, Schapiro NE, et al. The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells[J]. J Immunol, 2013, 190(3):1372-1379.
7.	Gabitass RF, Annels NE, Stocken DD, et al. Elevated myeloidderived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13[J]. Cancer Immunol Immunother, 2011, 60(10):1419-1430.
8.	Basso D, Fogar P, Falconi M, et al. Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen:role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study[J]. PLoS One, 2013, 8(1):e54824.
9.	Porembka MR, Mitchem JB, Belt BA, et al. Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth[J]. Cancer Immunol Immunother, 2012, 61(9):1373-1385.
10.	Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer[J]. Nature, 2010, 467(7319):1114-1117.
11.	Yang L, Debusk LM, Fukuda K, et al. Expansion of myeloid immune suppressor Gr⁺CD11b⁺ cells in tumor-bearing host directly promotes tumor angiogenesis[J]. Cancer Cell, 2004, 6(4): 409-421.
12.	Du R, Lu KV, Petritsch C, et al. HIF1αinduces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion[J]. Cancer Cell, 2008, 13(3): 206-220.
13.	袁田, 廖泉, 赵玉沛.吉西他滨代谢酶与胰腺癌化疗耐药关系的研究进展[J].中国普外基础与临床杂志, 2009, 16(8): 613-616.
14.	Nakasone ES, Askautrud HA, Kees T, et al. Imaging tumorstroma interactions during chemotherapy reveals contributions of the microenvironment to resistance[J]. Cancer Cell, 2012, 21(4):488-503.
15.	Le HK, Graham L, Cha E, et al. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice[J]. Int Immunopharmacol, 2009, 9(7/8):900-909.
16.	Ghansah T, Vohra N, Kinney K, et al. Chemoimmunotherapy provides protective immunity of murine pancreatic cancer model (P2070)[J]. J Immunol, 2013, 190(Meeting Abstract Supplement):132.25.
17.	Bunt SK, Mohr AM, Bailey JM, et al. Rosiglitazone and gemcitabine in combination reduces immune suppression and modulates T cell populations in pancreatic cancer[J]. Cancer Immunol Immunother, 2013, 62(2):225-236.
18.	Bruchard M, Mignot G, Derangère V, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth[J]. Nat Med, 2013, 19(1):57-64.
19.	Dimou A, Syrigos KN, Saif MW. Overcoming the stromal barrier:technologies to optimize drug delivery in pancreatic cancer[J]. Ther Adv Med Oncol, 2012, 4(5):271-279.
20.	Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans[J]. Science, 2011, 331(624):1612-1616.
21.	Ostrand-Rosenberg S, Sinha P, Beury DW, et al. Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression[J]. Semin Cancer Biol, 2012, 22(4):275-281.
22.	Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer[J]. Science, 2009, 324(5933):1457-1461.
23.	Bayne LJ, Beatty GL, Jhala N, et al. Tumor-derived granulocytemacrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer[J]. Cancer Cell, 2012, 21(6):822-835.
24.	Pilon-Thomas S, Nelson N, Vohra N, et al. Murine pancreatic adenocarcinoma dampens SHIP-1 expression and alters MDSC homeostasis and function[J]. PLoS One, 2011, 6(11):e27729.
25.	Mace TA, Ameen Z, Collins A, et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner[J]. Cancer Res, 2013, 73(10):3007-3018.
26.	Curtis VF, Wang H, Yang P, et al. A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer[J]. PLoS One, 2013, 8(1):e54916.
27.	Thakur A, Schalk D, Tomaszewski E, et al. Microenvironment generated during EGFR targeted killing of pancreatic tumor cells by ATC inhibits myeloid-derived suppressor cells through COX2 and PGE2 dependent pathway[J]. J Transl Med, 2013, 11:35.

1. Hidalgo M. Pancreatic cancer[J]. N Engl J Med, 2010, 362(17):1605-1617.
2. Vincent A, Herman J, Schulick R, et al. Pancreatic cancer[J]. Lancet, 2011, 378(9791):607-620.
3. Apte MV, Wilson JS, Lugea A, et al. A starring role for stellate cells in the pancreatic cancer microenvironment[J]. Gastroenterology, 2013, 144(6):1210-1219.
4. Talmadge JE, Gabrilovich DI. History of myeloid-derived suppressor cells[J]. Nat Rev Cancer, 2013, 13(10):739-752.
5. Zhao F, Obermann S, von Wasielewski R, et al. Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma[J]. Immunology, 2009, 128(1): 141-149.
6. Vernon PJ, Loux TJ, Schapiro NE, et al. The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells[J]. J Immunol, 2013, 190(3):1372-1379.
7. Gabitass RF, Annels NE, Stocken DD, et al. Elevated myeloidderived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13[J]. Cancer Immunol Immunother, 2011, 60(10):1419-1430.
8. Basso D, Fogar P, Falconi M, et al. Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen:role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study[J]. PLoS One, 2013, 8(1):e54824.
9. Porembka MR, Mitchem JB, Belt BA, et al. Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth[J]. Cancer Immunol Immunother, 2012, 61(9):1373-1385.
10. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer[J]. Nature, 2010, 467(7319):1114-1117.
11. Yang L, Debusk LM, Fukuda K, et al. Expansion of myeloid immune suppressor Gr⁺CD11b⁺ cells in tumor-bearing host directly promotes tumor angiogenesis[J]. Cancer Cell, 2004, 6(4): 409-421.
12. Du R, Lu KV, Petritsch C, et al. HIF1αinduces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion[J]. Cancer Cell, 2008, 13(3): 206-220.
13. 袁田, 廖泉, 赵玉沛.吉西他滨代谢酶与胰腺癌化疗耐药关系的研究进展[J].中国普外基础与临床杂志, 2009, 16(8): 613-616.
14. Nakasone ES, Askautrud HA, Kees T, et al. Imaging tumorstroma interactions during chemotherapy reveals contributions of the microenvironment to resistance[J]. Cancer Cell, 2012, 21(4):488-503.
15. Le HK, Graham L, Cha E, et al. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice[J]. Int Immunopharmacol, 2009, 9(7/8):900-909.
16. Ghansah T, Vohra N, Kinney K, et al. Chemoimmunotherapy provides protective immunity of murine pancreatic cancer model (P2070)[J]. J Immunol, 2013, 190(Meeting Abstract Supplement):132.25.
17. Bunt SK, Mohr AM, Bailey JM, et al. Rosiglitazone and gemcitabine in combination reduces immune suppression and modulates T cell populations in pancreatic cancer[J]. Cancer Immunol Immunother, 2013, 62(2):225-236.
18. Bruchard M, Mignot G, Derangère V, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth[J]. Nat Med, 2013, 19(1):57-64.
19. Dimou A, Syrigos KN, Saif MW. Overcoming the stromal barrier:technologies to optimize drug delivery in pancreatic cancer[J]. Ther Adv Med Oncol, 2012, 4(5):271-279.
20. Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans[J]. Science, 2011, 331(624):1612-1616.
21. Ostrand-Rosenberg S, Sinha P, Beury DW, et al. Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression[J]. Semin Cancer Biol, 2012, 22(4):275-281.
22. Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer[J]. Science, 2009, 324(5933):1457-1461.
23. Bayne LJ, Beatty GL, Jhala N, et al. Tumor-derived granulocytemacrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer[J]. Cancer Cell, 2012, 21(6):822-835.
24. Pilon-Thomas S, Nelson N, Vohra N, et al. Murine pancreatic adenocarcinoma dampens SHIP-1 expression and alters MDSC homeostasis and function[J]. PLoS One, 2011, 6(11):e27729.
25. Mace TA, Ameen Z, Collins A, et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner[J]. Cancer Res, 2013, 73(10):3007-3018.
26. Curtis VF, Wang H, Yang P, et al. A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer[J]. PLoS One, 2013, 8(1):e54916.
27. Thakur A, Schalk D, Tomaszewski E, et al. Microenvironment generated during EGFR targeted killing of pancreatic tumor cells by ATC inhibits myeloid-derived suppressor cells through COX2 and PGE2 dependent pathway[J]. J Transl Med, 2013, 11:35.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Progress of Myeloid Derived Suppressor Cells and Pancreatic Cancer

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