Tumor-reprogrammed resident T cells resist radiation to control tumors.
Animals
Cell Line, Tumor
Cell Movement
/ genetics
Cell Survival
/ genetics
Combined Modality Therapy
Gene Expression Profiling
/ methods
Immunotherapy
/ methods
Interferon-gamma
/ immunology
Lymphocytes, Tumor-Infiltrating
/ immunology
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neoplasms, Experimental
/ genetics
Radiation Tolerance
/ genetics
Radiotherapy
/ methods
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 09 2019
02 09 2019
Historique:
received:
15
12
2018
accepted:
06
08
2019
entrez:
4
9
2019
pubmed:
4
9
2019
medline:
31
12
2019
Statut:
epublish
Résumé
Successful combinations of radiotherapy and immunotherapy depend on the presence of live T cells within the tumor; however, radiotherapy is believed to damage T cells. Here, based on longitudinal in vivo imaging and functional analysis, we report that a large proportion of T cells survive clinically relevant doses of radiation and show increased motility, and higher production of interferon gamma, compared with T cells from unirradiated tumors. Irradiated intratumoral T cells can mediate tumor control without newly-infiltrating T cells. Transcriptomic analysis suggests T cell reprogramming in the tumor microenvironment and similarities with tissue-resident memory T cells, which are more radio-resistant than circulating/lymphoid tissue T cells. TGFβ is a key upstream regulator of T cell reprogramming and contributes to intratumoral Tcell radio-resistance. These findings have implications for the design of radio-immunotherapy trials in that local irradiation is not inherently immunosuppressive, and irradiation of multiple tumors might optimize systemic effects of radiotherapy.
Identifiants
pubmed: 31477729
doi: 10.1038/s41467-019-11906-2
pii: 10.1038/s41467-019-11906-2
pmc: PMC6718618
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3959Subventions
Organisme : NCI NIH HHS
ID : R01 CA134563
Pays : United States
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