CCR5-dependent homing of T regulatory cells to the tumor microenvironment contributes to skin squamous cell carcinoma development
| Autor: | Thaís Helena Gasparoto, João Santana da Silva, Ramon Kaneno, Maria Renata Sales Nogueira, Carine Ervolino de Oliveira, Ana Paula Campanelli, Vanessa Soares Lara, Nádia Ghinelli Amôr, Claudia Ramos Pinheiro, Gustavo Pompermaier Garlet, Karen A. Cavassani |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Adoptive cell transfer Chemokine Skin Neoplasms Receptors CCR5 Biology T-Lymphocytes Regulatory Mice 03 medical and health sciences 0302 clinical medicine Immune system Tumor Microenvironment Skin Squamous Cell Carcinoma Animals Humans Cytotoxic T cell IL-2 receptor Tumor microenvironment virus diseases 030104 developmental biology Oncology 030220 oncology & carcinogenesis Immunology Carcinoma Squamous Cell Cancer research biology.protein CAMUNDONGOS CD8 |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5- and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice. Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. Moreover, the adoptive transfer of naturally occurring Tregs CD4+CD25+CCR5+, CD4+CD25−CCR5+ or CD8+CCR5+ conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. Interestingly, adoptive transfer of WT CD4+CD25+CCR5+ cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8+ T cells. Our findings reinforce the therapeutic potential of CCR5 inhibition for cancer treatment, and indicate an attractive approach for SCC treatment. Mol Cancer Ther; 16(12); 2871–80. ©2017 AACR. |
| Databáze: | OpenAIRE |
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