title: INFα-2b inhibitory effects on CD4(+)CD25(+)FOXP3(+) regulatory T cells in the tumor microenvironment of C57BL/6 J mice with melanoma xenografts.
abstract: Regulatory T cells (Tregs), particularly the CD4(+)CD25(+)Foxp3(+) Tregs, down regulate immunity and promote tumor cell growth by directly suppressing CD8(+) and CD4(+) T cells. Alternatively they can promote tumor growth by generating interleukin-10 (IL-10) and transforming growth factor β (TGFβ) in situ, which help tumor cells to evade the immune system.
  
  
  
  In vivo tumor models were prepared via subcutaneous injection with a suspension of B16 melanoma cells into the left upper flank of C57BL/6 J mice. The mice were randomized into five groups: radiotherapy (RT), chemotherapy (CT), radiochemotherapy (RCT), Inteferon α (INFα) groups, and a control group. Flow cytometry was used to determine the Tregs levels in the spleen and peripheral blood, and immunohistochemistry was performed to determine the expression levels of TGFβ and IL-10 in the tumor microenvironment.
  
  
  
  Tumor weight was significantly reduced in the CT or RCT groups (40.91 % and 41.83 %, respectively), while the reduction in tumor weight was relatively lower for the RT and IFNα groups (15.10 % and 13.15 %, respectively). The flow cytometry results showed that the ratios of CD4(+)CD25(+)Foxp3(+) Tregs to lymphocytes and CD4(+) cells in the spleen and in peripheral blood were significantly decreased after treatment with IFNα (P < 0.05). Expression of TGFβ and IL-10 in the tumor microenvironment in the CT and RT groups was higher compared with the control group (P < 0.01), while the expression of TGFβ and IL-10 in the INFα group was not significantly different (P > 0.05).
  
  
  
  The results show that INFα-2b inhibits cancer cell immune evasion by decreasing the levels of CD4(+)CD25(+)Foxp3(+) Tregs and suppressing the expression of TGFβ and IL-10 in the tumor microenvironment.
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Breast Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Run
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Breast Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. tigerzong@msn.com.
authors.forename: Xiangyun
authors.identifier: 0000-0002-8673-9003
authors.initials: X
authors.lastname: Zong
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Mo
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D004358:Drug Therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy; D051379:Mice; D011897:Random Allocation; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D016898:Interferon-alpha; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: CD4+CD25+Foxp3+ Tregs; Chemotherapy; Immunotherapy; Melanoma; Tumor microenvironment