Pre-operative intracellular glutathione levels of peripheral monocytes as a biomarker to predict survival of colorectal cancer patients

作者: Kazuko Uno , Kiyotaka Okuno , Takuma Kato , Saeko Tada-Oikawa , Norimichi Kan

DOI: 10.1007/S00262-010-0868-3

关键词: Biomarker (medicine)MedicinePathologyMonocyteCancerCD14Survival analysisImmune systemImmunotherapyCancer researchColorectal cancerImmunologyImmunology and AllergyOncology

摘要: The ability to predict anti-tumor immune responses at local tumor growing sites using only peripheral blood specimens would be helpful in determining therapeutic options for patients with solid tumors. Here, we show that the glutathione intracellular content (icGSH) of monocytes (Mo) correlates positively T cell infiltration within islets and overall survival colorectal carcinoma. IcGSH redox status was determined CD14+ Mo prior surgery by staining monochlorobimane. tumor-infiltrating cells (TIL) were quantified as CD45RO+ resected tumors paraffin sections. A positive association found between GSH index TIL (P < 0.001). 50% cut-off value index, is determinant presence or absence islets, calculated almost 0.7 through logistic regression analysis. a ≥0.7 termed reductive (R)-Mo, those <0.7 designated oxidative (O)-Mo. Cox’s proportional hazards analysis R-Mo O-Mo surgery, TIL, correlate significantly rate stage II III patients. Kaplan–Meier also showed significant correlation. These results indicate icGSH useful biomarker parameter better understanding host/tumor relationship thereby enabling development an individual patient-oriented strategy.

参考文章(30)
Kazuko Uno, Yoko Mitsuishi, Mari Tanigawa, Kiyotaka Okuno, Norihiko Hirai, Youichi Mizutani, Hideo Saotome, Hiromi Fujiwara, Tsunataro Kishida, A series of immune responses leading to the induction ofT cell IL-12/IL-18 responsiveness in patientswith relatively large tumor burdens Cancer Immunology, Immunotherapy. ,vol. 52, pp. 33- 40 ,(2003) , 10.1007/S00262-002-0329-8
Alberto Mantovani, Silvano Sozzani, Massimo Locati, Tiziana Schioppa, Alessandra Saccani, Paola Allavena, Antonio Sica, Infiltration of tumours by macrophages and dendritic cells: tumour-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Novartis Foundation symposium. ,vol. 256, pp. 137- 148 ,(2004) , 10.1002/0470856734.CH10
C M Liang, N Lee, D Cattell, S M Liang, Glutathione Regulates Interleukin-2 Activity on Cytotoxic T-cells Journal of Biological Chemistry. ,vol. 264, pp. 13519- 13523 ,(1989) , 10.1016/S0021-9258(18)80027-8
Subhra K. Biswas, Antonio Sica, Claire E. Lewis, Plasticity of Macrophage Function during Tumor Progression: Regulation by Distinct Molecular Mechanisms Journal of Immunology. ,vol. 180, pp. 2011- 2017 ,(2008) , 10.4049/JIMMUNOL.180.4.2011
Anjali Desai, Jeffrey S. Warren, Xiaodong Huang, Intracellular glutathione redox status modulates MCP-1 expression in pulmonary granulomatous vasculitis. Laboratory Investigation. ,vol. 79, pp. 837- 847 ,(1999)
Hiroshi Nagura, Haruo Ohtani, Akio Ohuchi, Kenichi Shiiba, Yoshitaka Naito, Kazuya Saito, Katsunori Saigenji, CD8+ T Cells Infiltrated within Cancer Cell Nests as a Prognostic Factor in Human Colorectal Cancer Cancer Research. ,vol. 58, pp. 3491- 3494 ,(1998)
Fernando O. Martinez, Siamon Gordon, Massimo Locati, Alberto Mantovani, Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression Journal of Immunology. ,vol. 177, pp. 7303- 7311 ,(2006) , 10.4049/JIMMUNOL.177.10.7303
Kazuko Uno, Mayumi Hirosaki, Kazuhiro Kakimi, Masumi Tominaga, Yoshiki Suginoshita, Goji Hasegawa, Michiaki Fukui, Naoto Nakamura, Taro Shirakawa, Tsunataro Kishida, Impaired IFN-α Production and the Risk of Cancer Development Journal of Interferon and Cytokine Research. ,vol. 27, pp. 1013- 1018 ,(2007) , 10.1089/JIR.2007.0047
Norimichi Kan, Hiroshi Kodama, Taisuke Hori, Atsushi Takenaka, Tadaki Yasumura, Hirofumi Kato, Hiroki Ogawa, Sumio Mukaihara, Takashi Kudo, Kiyoshi Ohsumi, Keiichi Mise, Intrapleural adaptive immunotherapy for breast cancer patients with cytologically-confirmed malignant pleural effusions: an analysis of 67 patients in Kyoto and Shiga Prefecture, Japan. Breast Cancer Research and Treatment. ,vol. 27, pp. 203- 210 ,(1993) , 10.1007/BF00665690
Koustav Sarkar, Anamika Bose, Krishnendu Chakraborty, Enamul Haque, Diptendu Ghosh, Shyamal Goswami, Tathagata Chakraborty, Subrata Laskar, Rathindranath Baral, Neem leaf glycoprotein helps to generate carcinoembryonic antigen specific anti-tumor immune responses utilizing macrophage-mediated antigen presentation. Vaccine. ,vol. 26, pp. 4352- 4362 ,(2008) , 10.1016/J.VACCINE.2008.06.048