A nonimmune function of T cells in promoting lung tumor progression Journal Article
| Authors: | Green, J. A.; Arpaia, N.; Schizas, M.; Dobrin, A.; Rudensky, A. Y. |
| Article Title: | A nonimmune function of T cells in promoting lung tumor progression |
| Abstract: | The involvement of effector T cells and regulatory T (T reg) cells in opposing and promoting solid organ carcinogenesis, respectively, is viewed as a shifting balance between a breach versus establishment of tolerance to tumor or self-antigens. We considered that tumor-associated T cells might promote malignancy via distinct mechanisms used by T cells in nonlymphoid organs to assist in their maintenance upon injury or stress. Recent studies suggest that T reg cells can participate in tissue repair in a manner separable from their immunosuppressive capacity. Using transplantable models of lung tumors in mice, we found that amphiregulin, a member of the epidermal growth factor family, was prominently up-regulated in intratumoral T reg cells. Furthermore, T cell-restricted amphiregulin deficiency resulted in markedly delayed lung tumor progression. This observed deterrence in tumor progression was not associated with detectable changes in T cell immune responsiveness or T reg and effector T cell numbers. These observations suggest a novel "nonimmune" modality for intratumoral T reg and effector T cells in promoting tumor growth through the production of factors normally involved in tissue repair and maintenance. © 2017 Green et al. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; flow cytometry; ki 67 antigen; cd8+ t lymphocyte; cell proliferation; animal cell; mouse; phenotype; animal; metabolism; animals; gene expression; tumor volume; lung neoplasms; animal experiment; animal model; protein; pathology; cell line, tumor; neovascularization, pathologic; vascularization; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; wound healing; lung tumor; regulatory t lymphocyte; immunology; lymphocyte activation; gamma interferon; t-lymphocytes, regulatory; disease progression; cd4+ t lymphocyte; tumor cell line; natural killer cell; cytokine production; immunomodulation; beta 2 microglobulin; tumor growth; cytotoxic t lymphocyte antigen 4; glucocorticoid induced tumor necrosis factor receptor; neovascularization (pathology); disease exacerbation; t lymphocyte subpopulation; lymphocyte function; amphiregulin; tumor necrosis factor; rna sequence; cancer transplantation; programmed death 1 receptor; deficiency; tumor microenvironment; tumor necrosis; immune status; priority journal; article; macrophage elastase; areg protein; fn1 protein; hpse protein; plau protein; areg protein, mouse; e0771 cell line |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 214 |
| Issue: | 12 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2017-12-04 |
| Start Page: | 3565 |
| End Page: | 3575 |
| Language: | English |
| DOI: | 10.1084/jem.20170356 |
| PUBMED: | 29038367 |
| PROVIDER: | scopus |
| PMCID: | PMC5716034 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 January 2018 -- Source: Scopus |
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