Tumor-reprogrammed resident T cells resist radiation to control tumors

• DOI: 10.1038/s41467-019-11906-2
• Publication Date: 2019-09-02T18:11:06Z
• Authors: Ainhoa Arina; Michael Beckett; Christian Fernandez; Wenxin Zheng; Sean Pitroda; Steven J. Chmura; Jason J. Luke; Martin Forde; Yuzhu Hou; Byron Burnette; Helena Mauceri; Israel Lowy; Tasha Sims; Nikolai Khodarev; Yang-Xin Fu; Ralph R. Weichsel...
• Keywords: Reprogramming; Ex vivo

Abstract Successful combinations of radiotherapy and immunotherapy depend on the presence live T cells within tumor; however, is believed to damage cells. Here, based longitudinal in vivo imaging functional analysis, we report that a large proportion survive clinically relevant doses radiation show increased motility, higher production interferon gamma, compared with from unirradiated tumors. Irradiated intratumoral can mediate tumor control without newly-infiltrating Transcriptomic analysis suggests cell reprogramming microenvironment similarities tissue-resident memory cells, which are more radio-resistant than circulating/lymphoid tissue TGFβ key upstream regulator contributes Tcell radio-resistance. These findings have implications for design radio-immunotherapy trials local irradiation not inherently immunosuppressive, multiple tumors might optimize systemic effects radiotherapy.