The Hedgehog inhibitor cyclopamine impairs the benefits of immunotherapy with activated T and NK lymphocytes derived from patients with advanced cancer
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- 作者：Hideya Onishi (1)
Takashi Morisaki (2)
Akifumi Kiyota (2)
Norihiro Koya (2)
Hiroto Tanaka (2)
Masayo Umebayashi (2)
Mitsuo Katano (1) - 关键词：Hedgehog signaling ; Cyclopamine ; Activated lymphocytes ; Advanced cancer ; Hypoxia
- 刊名：Cancer Immunology, Immunotherapy
- 出版年：2013
- 出版时间：June 2013
- 年：2013
- 卷：62
- 期：6
- 页码：1029-1039
- 全文大小：574KB
- 参考文献：1. Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15:3059-087 CrossRef
2. Cohen MM Jr (2003) The hedgehog signaling network. Am J Med Genet A 123:5-8 CrossRef
3. Pasca di Magliano M, Hebrok M (2003) Hedgehog signaling in cancer formation and maintenance. Nat Rev Cancer 3:903-11 CrossRef
4. Nagai S, Nakamura M, Yanai K, Wada J, Akiyoshi T, Nakashima H et al (2008) Gli1 contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase-9 activation. Cancer Sci 99:1377-384 CrossRef
5. Souzaki M, Kubo M, Kai M, Kameda C, Tanaka H, Taguchi T et al (2011) Hedgehog signaling pathway mediates the progression of non-invasive breast cancer to invasive breast cancer. Cancer Sci 102:373-81 CrossRef
6. Onishi H, Katano M (2011) Hedgehog signaling pathway as a therapeutic target in various types of cancer. Cancer Sci 102:1756-760 CrossRef
7. Tremblay MR, Nesler M, Weatherhead R, Castro AC (2009) Recent patents for hedgehog pathway inhibitors for the treatment of malignancy. Expert Opin Ther Pat 19:1039-056 CrossRef
8. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L et al (2009) Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361:1173-178 CrossRef
9. Tremblay MR, Lescarbeau A, Grogan MJ (2009) Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926). J Med Chem 52:4400-418 CrossRef
10. Low JA, de Sauvage FJ (2010) Clinical experience with hedgehog pathway inhibitors. J Clin Oncol 28:5321-326 CrossRef
11. Atwood SX, Chang AL, Oro AE (2012) Hedgehog pathway inhibition and the race against tumor evolution. J Cell Biol 199:193-97
12. Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:480-89 CrossRef
13. Dougan M, Dranoff G (2009) Immune therapy for cancer. Ann Rev Immunol 27:83-17 CrossRef
14. Onishi H, Morisaki T, Baba E, Nakamura M, Inaba S, Kuroki H et al (2011) Long-term vaccine therapy with autologous whole tumor cell-pulsed dendritic cells for a patient with recurrent rectal carcinoma. Anticancer Res 31:3995-005
15. Lowrey JA, Stewart GA, Lindey S, Hoyne GF, Dallman MJ, Howie SEM et al (2002) Sonic hedgehog promotes cell cycle progression in activated peripheral CD4+ T lymphocytes. J Immunol 169:1869-875
16. Stewart GA, Lowrey JA, Wakelin SJ, Fitch PM, Lindey S, Dallman MJ et al (2002) Sonic hedgehog signaling modulates activation of and cytokine production by human peripheral CD4+ T cells. J Immunol 169:5451-457
17. Rowbotham NJ, Hager-Theodorides AL, Furmanski AL, Crompton T (2007) A novel role for hedgehog in T-cell receptor signaling. Cell Cycle 17:2138-142 CrossRef
18. Syn WK, Witek RP, Curbishley SM, Jung Y, Choi SS, Enrich B et al (2009) Role for hedgehog pathway in regulating growth and function of invariant NKT cells. Eur J Immunol 39:1879-892 CrossRef
19. Radfar S, Wang Y, Khong HT (2009) Activated CD4+ T cells dramatically enhance chemotherapeutic tumor responses in vitro and in vivo. J Immunol 183:6800-807 CrossRef
20. Caldwell CC, Kojima H, Lukashev D, Armstrong J, Farber M, Apasov SG et al (2001) Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J Immunol 167:6140-149
21. Hockel S, Schlenger K, Vaupel P, Hockel M (2001) Association between host tissue vascularity and the prognostically relevant tumor vascularity in human cervical cancer. Int J Oncol 19:827-32
22. Ogino T, Onishi H, Suzuki H, Morisaki T, Tanaka M, Katano M (2012) Inclusive estimation of complex antigen presentation functions of monocyte-derived dendritic cells differentiated under normoxia and hypoxia conditions. Cancer Immunol Immunother 61:409-24 CrossRef
23. Lukashev D, Caldwell C, Ohta A, Chen P, Sitkovsky M (2001) Differential regulation of two alternatively spliced isoforms of hypoxia-inducible factor-1α in activated TNK lymphocytes. J Biol Chem 276:48754-8763 CrossRef
24. Lukashev D, Sitkovsky M (2008) Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1α in activated human T lymphocytes. Hum Immunol 69:421-25 CrossRef
25. Larbi A, Zelba H, Goldeck D, Pawelec G (2010) Induction of HIF-1α and the glycolytic pathway alters apoptotic and differentiation profiles of activated human T cells. J Leukoc Biol 87:265-73 CrossRef
26. Onishi H, Morisaki T, Baba E, Kuga H, Kuroki H, Matsumoto K et al (2002) Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer. Clin Immunol 105:286-95 CrossRef
27. Morisaki T, Onishi H, Koya N, Kiyota A, Tanaka H, Umebayashi M et al (2011) Combinational cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system. Anticancer Res 31:2505-510
28. Morisaki T, Onishi H, Katano M (2012) Cancer immunotherapy using NKG2D and DNAM-1 systems. Anticancer Res 32:2241-248
29. Onishi H, Morifuji Y, Kai M, Suyama K, Iwasaki H, Katano M (2012) Hedgehog inhibitor decreases chemosensitivity to 5-fluorouracil and gemcitabine under hypoxic conditions in pancreatic cancer. Cancer Sci 103:1272-279
30. Schwinn N, Vokhminova D, Sucker A, Textor S, Striegel S, Moll I et al (2009) Interferon-γ down-regulates NKG2D ligand expression and impairs the NKG2D-mediated cytolysis of MHC class I-deficient melanoma by natural killer cells. Int J Cancer 124:1594-604 CrossRef
31. Onishi H, Kai M, Odate S, Iwasaki H, Morifuji Y, Ogino T et al (2011) Hypoxia activates the hedgehog signaling pathway in a ligand-independent manner by upregulation of Smo transcription in pancreatic cancer. Cancer Sci 102:1144-150 CrossRef - 作者单位：Hideya Onishi (1)
Takashi Morisaki (2)
Akifumi Kiyota (2)
Norihiro Koya (2)
Hiroto Tanaka (2)
Masayo Umebayashi (2)
Mitsuo Katano (1)
1. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
2. Fukuoka General Cancer Clinic, Fukuoka, Japan - ISSN：1432-0851
文摘
Hedgehog (Hh) signaling is activated in various types of cancer and contributes to the progression, proliferation, and invasiveness of cancer cells. Many Hh inhibitors are undergoing clinical trial and show promise as anticancer drugs. Hh signaling is also induced in the activated T and NK (TNK) lymphocytes that are used in immunotherapy. Activated TNK lymphocyte therapy is anticipated to work well within a tumor’s hypoxic environment. However, most studies on the immunobiological functions of activated TNK lymphocytes have been conducted on healthy donor samples, under normoxic conditions. In the present study, we evaluated the effects of Hh inhibition and oxygen concentrations on the function of activated TNK lymphocytes derived from patients with advanced cancer. Proliferation, migration, surface NKG2D expression, and cytotoxicity were all significantly inhibited, and IFN-γ secretion was significantly increased upon Hh inhibitor treatment of activated TNK lymphocytes under hypoxic conditions in vitro. Tumors from mice injected with cyclopamine-treated activated TNK lymphocytes showed a significant increase in tumor size and had fewer apoptotic cells compared with the tumors in mice injected with control activated TNK lymphocytes. These results suggest that Hh signaling plays a pivotal role in activated TNK lymphocyte cell function. Combination therapy using Hh inhibitors and activated TNK lymphocytes derived from patients with advanced cancer may not be advantageous.