The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche
Open accessAbstract
Summary Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung, but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4+-regulatory T (Treg) cell induction, and restrain CD8+ T cell effector function. Tumor colonization is accompanied by PHD protein-dependent induction of pulmonary Treg cells and suppression of IFN-γ-dependent tumor clearance. T cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis.
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Metadata
- Authors
- Clever, D., Roychoudhuri, R., Constantinides, M. G., Askenase, M. H., Sukumar, M., Klebanoff, C. A., Eil, R. L., Hickman, H. D., Yu, Z., Pan, J. H., Palmer, D. C., Phan, A. T., Goulding, J., Gattinoni, L., Goldrath, A. W., Belkaid, Y., & Restifo, N. P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 166
- Issue
- 5
- Pages
- 1117-1131.e14
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2510836433
- Cited by
- 242
- References
- 18
- FWCI
- 15.14
- Type
- journal article
- Language
- en
- Open access
- bronze
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