Two FOXP3+CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers
| العنوان: | Two FOXP3+CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers |
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| المؤلفون: | Shimon Sakaguchi, Masahira Hattori, Koji Atarashi, Takeshi Tanoue, Hiroyoshi Nishikawa, Hirofumi Yamamoto, Hirotsugu Nagase, Takuro Saito, Junichi Nishimura, Kenya Honda, Shuji Takiguchi, Eiichi Sato, Daisuke Sugiyama, Yuichiro Doki, Hidetoshi Morita, Masaki Mori, Wataru Suda, Yuji Nagano, Yuka Maeda, Hisashi Wada, Masahide Hamaguchi, Naganari Ohkura |
| المصدر: | Nature Medicine. 22:679-684 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Colorectal cancer, T cell, Biology, T-Lymphocytes, Regulatory, Interleukin-12 Subunit p35, General Biochemistry, Genetics and Molecular Biology, Transforming Growth Factor beta1, 03 medical and health sciences, Interleukin 21, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, T-Lymphocyte Subsets, medicine, Humans, Cytotoxic T cell, Survival rate, Digestive System Surgical Procedures, Aged, Neoplasm Staging, Aged, 80 and over, Cd4 t cell, FOXP3, Forkhead Transcription Factors, General Medicine, Middle Aged, Prognosis, medicine.disease, Survival Rate, 030104 developmental biology, medicine.anatomical_structure, Immunology, Cancer research, Female, Colorectal Neoplasms, Tumor immunology, 030215 immunology |
| الوصف: | CD4(+) T cells that express the forkhead box P3 (FOXP3) transcription factor function as regulatory T (Treg) cells and hinder effective immune responses against cancer cells. Abundant Treg cell infiltration into tumors is associated with poor clinical outcomes in various types of cancers. However, the role of Treg cells is controversial in colorectal cancers (CRCs), in which FOXP3(+) T cell infiltration indicated better prognosis in some studies. Here we show that CRCs, which are commonly infiltrated by suppression-competent FOXP3(hi) Treg cells, can be classified into two types by the degree of additional infiltration of FOXP3(lo) nonsuppressive T cells. The latter, which are distinguished from FOXP3(+) Treg cells by non-expression of the naive T cell marker CD45RA and instability of FOXP3, secreted inflammatory cytokines. Indeed, CRCs with abundant infiltration of FOXP3(lo) T cells showed significantly better prognosis than those with predominantly FOXP3(hi) Treg cell infiltration. Development of such inflammatory FOXP3(lo) non-Treg cells may depend on secretion of interleukin (IL)-12 and transforming growth factor (TGF)-β by tissues and their presence was correlated with tumor invasion by intestinal bacteria, especially Fusobacterium nucleatum. Thus, functionally distinct subpopulations of tumor-infiltrating FOXP3(+) T cells contribute in opposing ways to determining CRC prognosis. Depletion of FOXP3(hi) Treg cells from tumor tissues, which would augment antitumor immunity, could thus be used as an effective treatment strategy for CRCs and other cancers, whereas strategies that locally increase the population of FOXP3(lo) non-Treg cells could be used to suppress or prevent tumor formation. |
| تدمد: | 1546-170X 1078-8956 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a98892e49e6e78eef7d658f624cd8bbf https://doi.org/10.1038/nm.4086 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....a98892e49e6e78eef7d658f624cd8bbf |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1546170X 10788956 |
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