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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 3/2014

01-03-2014 | Research Article

Changes in the immune cell population and cell proliferation in peripheral blood after gemcitabine-based chemotherapy for pancreatic cancer

Authors: Y. Homma, K. Taniguchi, M. Nakazawa, R. Matsuyama, R. Mori, K. Takeda, Y. Ichikawa, K. Tanaka, I. Endo

Published in: Clinical and Translational Oncology | Issue 3/2014

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Abstract

Purpose

Regulatory T cells (Tregs) play a role in the immunosuppressive state in pancreatic cancer patients. We aimed to evaluate the changes of immune cells population including Tregs caused by gemcitabine (GEM)-based chemotherapy.

Methods

Fifty-three patients with pancreatic cancer were enrolled in this study, of which 32 received GEM- based chemotherapy. Blood samples were collected before and at least 2 weeks after the last dose of chemotherapy. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Other lymphocytes and NK cell markers were also measured. The proliferative capacity of PBMCs stimulated with anti-CD3 was analyzed using H3 thymidine.

Results

The percentage and number of Tregs were significantly decreased after chemotherapy (p = 0.032, p = 0.003, respectively). The other immune cells and the proliferative capacity did not change.

Conclusion

This study showed that GEM-based chemotherapy produced an immunomodulatory effect via the depletion of Tregs.
Literature
1.
2.
Wray CJ, Ahmad SA, Matthews JB, Lowy AM. Surgery for pancreatic cancer: recent controversies and current practice. Gastroenterology. 2005;128:1626–41.PubMedCrossRef
3.
Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvement in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.PubMed
4.
Ozaka M, Matsumura Y, Ishii H, Omuro Y, Itoi T, Mouri H, et al. Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study). Cancer Chemother Pharmacol. 2012;69:1197–204.PubMedCrossRef
5.
Plate JM, Plate AE, Shott S, Bograd S, Harris JE. Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas. Cancer Immunol Immunother. 2005;54:915–25.PubMedCrossRef
6.
Thornton AM, Shevach EM. CD4;CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med. 1998;188:287–96.PubMedCentralPubMedCrossRef
7.
8.
Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A. CD4+CD25+regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer. 2003;98:1089–99.PubMedCrossRef
9.
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942–9.PubMedCrossRef
10.
Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res. 2005;65:2457–64.PubMedCrossRef
11.
Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–61.PubMed
12.
Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001;61:4766–72.PubMed
13.
Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Shlom J, et al. Enhanced functionality of CD4+CD25(high) Foxp3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res. 2008;14:1032–40.PubMedCrossRef
14.
Chang WC, Li CH, Huang SC, Chang DY, Chou LY, Shue BC. Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma. Cancer. 2010;116:5777–88.PubMedCrossRef
15.
Liotta F, Gacci M, Frosali F, Querci V, Vittori G, Lapini A, et al. Frequency of regulatory T cells in peripheral blood and in tumor-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma. BJU Int. 2011;107:1500–6.PubMedCrossRef
16.
Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of Foxp3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006;12:5423–34.PubMedCrossRef
17.
Ikemoto T, Yamaguchi T, Morine Y, Imura S, Soejima Y, Fujii M, et al. Clinical roles of increased populations of Foxp3+CD4+ T cells in peripheral blood from advanced pancreatic cancer patients. Pancreas. 2006;33:386–90.PubMedCrossRef
18.
Sobin LH, Wittekind CL, editors. TNM classification of malignant tumors. 6th ed. New York: John Wiley & Sons, Inc.; 2002.
19.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRef
20.
Marigo I, Dolcetti L, Serafini P, Zanovello P, Bronte V. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev. 2008;222:162–79.PubMedCrossRef
21.
Rosenberg SO. Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother. 2000;59:1593–600.CrossRef
22.
Sojka DK, Donepudi M, Bluestone JA, Mokyr MB. Melphalan and other anticancer modalities up-regulate B7-1 gene expression in tumor cells. J Immunol. 2000;164:6230–6.PubMed
23.
Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61.PubMedCrossRef
24.
Zhang L, Dermawan K, Jin M, Liu R, Zheng H, Xu L, et al. Differential impairment of regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy. Clin Immunol. 2008;129:219–29.PubMedCrossRef
25.
26.
27.
Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, et al. 5-Fluouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 2010;70:3052–61.PubMedCrossRef
28.
Nowak AK, Robbinson BW, Lake RA. Gemcitabine exerts a selective effect on the humoral immune response: Implications for combination chemo-immunotherapy. Cancer Res. 2002;62:2353–8.PubMed
29.
Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005;11:6713–21.PubMedCrossRef
30.
Rettig L, Seidenberg S, Parvanova I, Samaras P, Curioni A, Knuth A, et al. Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells. Int J Cancer. 2011;129:832–8.PubMedCrossRef
Metadata
Title
Changes in the immune cell population and cell proliferation in peripheral blood after gemcitabine-based chemotherapy for pancreatic cancer
Authors
Y. Homma
K. Taniguchi
M. Nakazawa
R. Matsuyama
R. Mori
K. Takeda
Y. Ichikawa
K. Tanaka
I. Endo
Publication date
01-03-2014
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 3/2014
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1079-0

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