TGF-β suppresses type 2 immunity to cancer Journal Article
| Authors: | Liu, M.; Kuo, F.; Capistrano, K. J.; Kang, D.; Nixon, B. G.; Shi, W.; Chou, C.; Do, M. H.; Stamatiades, E. G.; Gao, S.; Li, S.; Chen, Y.; Hsieh, J. J.; Hakimi, A. A.; Taniuchi, I.; Chan, T. A.; Li, M. O. |
| Article Title: | TGF-β suppresses type 2 immunity to cancer |
| Abstract: | The immune system uses two distinct defence strategies against infections: microbe-directed pathogen destruction characterized by type 1 immunity1, and host-directed pathogen containment exemplified by type 2 immunity in induction of tissue repair2. Similar to infectious diseases, cancer progresses with self-propagating cancer cells inflicting host-tissue damage. The immunological mechanisms of cancer cell destruction are well defined3–5, but whether immune-mediated cancer cell containment can be induced remains poorly understood. Here we show that depletion of transforming growth factor-β receptor 2 (TGFBR2) in CD4+ T cells, but not CD8+ T cells, halts cancer progression as a result of tissue healing and remodelling of the blood vasculature, causing cancer cell hypoxia and death in distant avascular regions. Notably, the host-directed protective response is dependent on the T helper 2 cytokine interleukin-4 (IL-4), but not the T helper 1 cytokine interferon-γ (IFN-γ). Thus, type 2 immunity can be mobilized as an effective tissue-level defence mechanism against cancer. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | cancer survival; controlled study; protein expression; interferon; cancer growth; cancer risk; nonhuman; transcription factor foxp3; cd8+ t lymphocyte; animal cell; mouse; animal tissue; cell death; breast cancer; tumor volume; interleukin 4; animal experiment; animal model; transgenic mouse; scleroprotein; granzyme b; regulatory t lymphocyte; th2 cell; immune response; cancer cell; cd4+ t lymphocyte; adoptive transfer; tumor immunity; cell hypoxia; th1 cell; tumor growth; cytotoxic t lymphocyte antigen 4; malignant transformation; tissue injury; t lymphocyte activation; tissue repair; collagen type 4; fibronectin; programmed death 1 receptor; mouse model; transforming growth factor beta receptor 2; infection resistance; vascular remodeling; cell destruction; lymphocyte transfer; female; priority journal; article |
| Journal Title: | Nature |
| Volume: | 587 |
| Issue: | 7832 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-11-05 |
| Start Page: | 115 |
| End Page: | 120 |
| Language: | English |
| DOI: | 10.1038/s41586-020-2836-1 |
| PUBMED: | 33087928 |
| PROVIDER: | scopus |
| PMCID: | PMC8347705 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
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