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Surgical influence of pancreatectomy on the function and count of circulating dendritic cells in patients with pancreatic cancer

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Abstract

Background: Dendritic cells (DCs) are important for an immune surveillance. Myeloid DCs (DC1) are important for an effective antitumor immune system. The function and count of circulating DC1 (cDC1) in hosts with a malignant tumor would be defective. This study focused on analyzing the immunological features of cDC1 in patients with pancreatic cancer during the perioperative period. Materials and methods: Thirty-two pancreatic cancer patients who underwent pancreatectomy and 18 age-matched healthy individuals as controls were enrolled in this study. The perioperative cDC count, the stimulatory capacity of cDC1 against allogeneic T cells and TGF-β1 level in the serum were measured. The cDC count was measured at 12 months after the operation. Results: The preoperative cDC1/cDC2 ratio, cDC1 count, and stimulatory capacity of cDC1 were impaired in patients in comparison to controls (P<0.05). The serum TGF-β1 level was significantly higher in patients than controls (P<0.001). The stimulatory capacity of cDC1 recovered after pancreatectomy (P<0.05). The serum TGF-β1 level significantly decreased after the operation (P<0.05); however, they were still significantly higher than controls (P<0.05). Although the cDC1/cDC2 ratio and the cDC1 count did not increase after the pancreatectomy, they recovered as the controls’ level at 12 months after the pancreatectomy in disease-free patients (P<0.05) and the serum TGF-β1 level in those patients at 12 months after the operation significantly decreased compared with those at the postoperative period (P<0.05). Conclusion: Surgical resection of pancreatic cancer could be associated with improved cDC1 function. When a patient remained disease free, the recovery of cDC1 counts was observed approximately 12 months after pancreatectomy. Further strategy will be needed to improve immune function in patients with pancreatic cancer.

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References

  1. Lillemoe KD, Cameron JL, Yeo CJ, Sohn TA, Nakeeb A, Sauter PK, Hruban RH, Abrams RA, Pitt HA (1996) Pancreaticoduodenectomy. Does it have a role in the palliation of pancreatic cancer? Ann Surg 223:718–728

    Article  PubMed  CAS  Google Scholar 

  2. Health and Welfare Statistics Association (2004) J Health Welfare Stat 51:45–56

    Google Scholar 

  3. Takai S, Satoi S, Toyokawa H, Yanagimoto H, Sugimoto N, Tsuji K, Araki H, Matsui Y, Imamura A, Kwon AH, Kamiyama Y (2003) Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: a retrospective, single-institution experience. Pancreas 26:243–249

    Article  PubMed  CAS  Google Scholar 

  4. von Bernstorff W, Voss M, Freichel S, Schmid A, Vogel I, Johnk C, Henne-Bruns D, Kremer B, Kalthoff H (2001) Systemic and local immunosuppression in pancreatic cancer patients. Clin Cancer Res 7:925–932

    Google Scholar 

  5. Ito T, Inaba M, Inaba K, Toki J, Sogo S, Iguchi T, Adachi Y, Yamaguchi K, Amakawa R, Valladeau J, Saeland S, Fukuhara S, Ikehara S (1999) A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells. J Immunol 163:1409–1419

    PubMed  CAS  Google Scholar 

  6. O’Doherty U, Peng M, Gezelter S, Swiggard WJ, Betjes M, Bhardwaj N, Steinman RM (1994) Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 82:487–493

    PubMed  CAS  Google Scholar 

  7. Ito T, Amakawa R, Inaba M, Ikehara S, Inaba K, Fukuhara S (2001) Differential regulation of human blood dendritic cell subsets by IFNs. J Immunol 166:2961–2969

    PubMed  CAS  Google Scholar 

  8. Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immun 9:271–296

    Article  PubMed  CAS  Google Scholar 

  9. Klein L, Trautman L, Psarras S, Schnell S, Siermann A, Liblau R, Boehmer H, Khazaie K (2003) Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor. Eur J Immunol 33:806–814

    Article  PubMed  CAS  Google Scholar 

  10. Yanagimoto H, Takai S, Satoi S, Toyokawa H, Takahashi K, Terakawa N, Kwon AH, Kamiyama Y (2005) Impaired function of circulating dendritic cells in patients with pancreatic cancer. Clin Immunol 114:52–60

    Article  PubMed  CAS  Google Scholar 

  11. Sobin LH, Wittekind CH (eds) (2002) TNM classificeation of malignant tumors, 6th edn. Wiley, New York

    Google Scholar 

  12. Toyokawa H, Inaba M, Takai S, Satoi S, Beuth J, Ko HL, Matsui Y, Kwon AH, Kamiyama Y, Ikehara S (2002) Enhancement of circulating dendritic cell activity by immunomodulators (OK432 and KP-40). Anticancer Res 22:2137–2145

    PubMed  CAS  Google Scholar 

  13. Huang A, Gilmour JW, Imami N, Amjadi P, Henderson DC, Allen-Mersh TG (2003) Increased serum transforming growth factor-beta1 in human colorectal cancer correlates with reduced circulating dendritic cells and increased colonic Langerhans cell infiltration. Clin Exp Immunol 134:270–278

    Article  PubMed  CAS  Google Scholar 

  14. Kobie JJ, Wu RS, Kurt RA, Lou S, Adelman MK, Whitesell LJ, Ramanathapuram LV, Arteaga CL, Akporiaye ET (2003) Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 63:1860–1864

    PubMed  CAS  Google Scholar 

  15. Dallal RM, Christakos P, Lee K, Egawa S, Son YI, Lotze MT (2002) Paucity of dendritic cells in pancreatic cancer. Surgery 131:135–138

    Article  PubMed  Google Scholar 

  16. Ungefroren H, Voss M, Bernstorff W, Schmid A, Kremer B, Kalthoff H (1999) Immunological escape mechanisms in pancreatic cancinoma. Ann Ny Acad Sci 880:243–251

    Article  PubMed  CAS  Google Scholar 

  17. Ohm JE, Gabrilovich DI, Sempowski GD, Kisseleva E, Parman KS, Nadaf S, Carbone DP (2003) VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood 101:4878–4886

    Article  PubMed  CAS  Google Scholar 

  18. Dong R, Cwynarski K, Entwistle A, Marelli-Berg F, Dazzi F, Simpson E, Goldman JM, Melo JV, Lechler RI, Bellantuono I, Ridley A, Lombardi G (2003) Dendritic cells from CML patients have altered actin organization, reduced antigen processing, and impaired migration. Blood 101:3560–3567

    Article  PubMed  CAS  Google Scholar 

  19. Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472

    Article  PubMed  CAS  Google Scholar 

  20. Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766

    PubMed  CAS  Google Scholar 

  21. Hoffmann TK, Muller-Berghaus J, Ferris RL, Johnson JT, Storkus WJ, Whiteside TL (2002) Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clin Cancer Res 8:1787–1793

    PubMed  Google Scholar 

  22. Ninomiya T, Akbar SM, Masumoto T, Horiike N, Onji M (1999) Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma. J Hepatol 31:323–331

    Article  PubMed  CAS  Google Scholar 

  23. Satthaporn S, Robins A, Vassanasiri W, El-Sheemy M, Jibril JA, Clark D, Valerio D, Eremin O (2004) Dendritic cells are dysfunctional in patients with operable breast cancer. Cancer Immunol Immunother 53:510–518

    Article  PubMed  Google Scholar 

  24. Tourkova IL, Yamabe K, Foster B, Chatta G, Perez L, Shurin GV, Shurin MR (2004) Murine prostate cancer inhibits both in vivo and in vitro generation of dendritic cells from bone marrow precursors. Prostate 59:203–213

    Article  PubMed  Google Scholar 

  25. Esche C, Gambotto A, Satoh Y, Gerein V, Robbins PD, Watkins SC, Lotze MT, Shurin MR (1999) CD154 inhibits tumor-induced apoptosis in dendritic cells and tumor growth. Eur J Immunol 29:2148–2155

    Article  PubMed  CAS  Google Scholar 

  26. Kiertscher SM, LUO J, Dubinett SM, Roth MD (2000) Tumors promote altered maturation and early apoptosis of monocyte derived dendritic cell. J Immunol 164:1269–1276

    PubMed  CAS  Google Scholar 

  27. Aalamian M, Pirtskhalaishvili G, Nunez A, Esche C, Shurin GV, Huland E, Huland H, Shurin MR (2001) Human prostate cancer regulates generation and maturation of monocyte derived dendritic cells. Prostate 46:68–75

    Article  PubMed  CAS  Google Scholar 

  28. Vakkila l, Thomson AW, Vettenranta K, Sariola H, Saarinen-Pihkala UM (2004) Dendritic cell subsets in childhood and in children with cancer: relation to age and disease prognosis. Clin Exp Immunol 135:455–461

    Article  PubMed  CAS  Google Scholar 

  29. Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, Liu YJ, Blazar BR,Chen W (2004) Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+regulatory T cells. J Immunol 173:4433–4442

    PubMed  CAS  Google Scholar 

  30. Kuwana M, Kaburaki J, Wright TM, Kawakami Y, Ikeda Y (2001) Induction of antigen-specific human CD4(+) Tcell anergy by peripheral blood DC2 precursors. Eur J Immunol 31:2547–2557

    Article  PubMed  CAS  Google Scholar 

  31. Lu L, McCaslin D, Starzl TE, Thomson AW (1995) Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7–1dim, B7–2) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes. Transplantation 60: 1539–1545

    Article  PubMed  CAS  Google Scholar 

  32. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192: 1213–1222

    Article  PubMed  CAS  Google Scholar 

  33. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238

    Article  PubMed  CAS  Google Scholar 

  34. Mazariegos GV, Zahorchak AF, Reyes J, Ostrowski L, Flynn B, Zeevi A, Thomson AW (2003) Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients. Am J Transplant 3: 689–696

    Article  PubMed  Google Scholar 

  35. Nozoe T, Korenaga D, Ohga T, Futatsugi M, Maehara Y (2003) Suppression of the phytohemagglutinin response to lymphocytes is an independent prognosticator in patients with squamous cell carcinoma of the esophagus. Ann Thorac Surg 76: 260–265

    Article  PubMed  Google Scholar 

  36. Farinas MC, Rodriguez-Valverde V, Zarrabeitia MT, Parra-Blanco JA, Sanz-Ortiz J (1991) Contribution of monocytes to the decreased lymphoproliferative response to phytohemagglutinin in patients with lung cancer. Cancer 68:1279–1284

    Article  PubMed  CAS  Google Scholar 

  37. Bauernhofer T, Kuss I, Henderson B, Baum AS, Whiteside TL (2003) Preferential apoptosis of CD56dim natural killer cell subset in patients with cancer. Eur J Immunol 33:119–124

    Article  PubMed  CAS  Google Scholar 

  38. Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Gold LI, Korc M (1993) Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 105:1846–1856

    PubMed  CAS  Google Scholar 

  39. Shim KS, Kim KH, Han WS, Park EB (1999) Elevated serum levels of transforming growth factor-beta1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection. Cancer 85:554–561

    Article  PubMed  CAS  Google Scholar 

  40. Shariat SF, Shalev M, Menesses-Diaz A, Kim IY, Kattan MW, Wheeler TM, Slawin KM (2001) Preoperative plasma levels of transforming growth factor beta1 (TGF-beta1) strongly predict progression in patients undergoing radical prostatectomy. J Clin Oncol 19:2856–2864

    PubMed  CAS  Google Scholar 

  41. Young MR, Wright MA, Lozano Y, Matthews JP, Benefield J, Prechel MM (1996) Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. Int J Cancer 67:333–338

    Article  PubMed  CAS  Google Scholar 

  42. Lin CM, Wang FH, Lee PK (2002) Activated human CD4+ T cells induced by dendritic cell stimulation are most sensitive to transforming growth factor-beta: implications for dendritic cell immunization against cancer. Clin Immunol 102:96–105

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We greatly thank Dr. M. Inaba (First Department of Pathology, Kansai Medical University) for his skillful technical assistance, Ms. S. Miura (First Department of Pathology, Kansai Medical University) for sorting cells on a FACStar, and Ms. A. Kihara (Department of Surgery, Kansai Medical University) for manuscript preparation.

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  1. Department of Surgery, Kansai Medical University, 10-15, Fumizono, Moriguchi, Osaka, 570-8507, Japan

    Kanji Takahashi, Hideyoshi Toyokawa, Soichiro Takai, Sohei Satoi, Hiroaki Yanagimoto, Naoyoshi Terakawa, Hiroshi Araki, A-Hon Kwon & Yasuo Kamiyama

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  1. Kanji Takahashi
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Takahashi, K., Toyokawa, H., Takai, S. et al. Surgical influence of pancreatectomy on the function and count of circulating dendritic cells in patients with pancreatic cancer. Cancer Immunol Immunother 55, 775–784 (2006). https://doi.org/10.1007/s00262-005-0079-5

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