Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients

September 2020 Science Eline Feenstra

Clinical studies combining radiation and immunotherapy have shown promising response rates. Therefore, there is an ongoing surge in trials using preconditioning regimens with immunotherapy. Yet, due to the scarcity of resected tumors treated in situ with radiotherapy, there has been little investigation of radiation’s sole contributions to local and systemic antitumor immunity in patients. To investigate the immune impact of radiation on the tumor microenvironment, a new study analyzed renal cell carcinomas from patients treated with stereotactic body radiation therapy.

So far, translational studies have been limited to evaluating circulating immune subsets and systemic remodeling of peripheral T cell receptor repertoires. This constraint has left gaps in how radiation impacts intratumoral responses and whether tumor-resident T cell clones are amplified following treatment. To test the hypothesis that radiation initiates local and systemic expansion of tumor-resident clones, the investigators analyzed renal cell carcinomas using bulk RNA-sequencing.

Radiaton increases clonality

Pathway analysis showed radiation-specific enrichment of immune-related processes, and T cell receptor sequencing revealed increased clonality in radiation-treated tumors. The results showed increased abundance of tumor-enriched clonotypes at 2 wk postradiation compared with pretreatment levels; however, this expansion was not sustained, and levels contracted toward baseline by 4 wk posttreatment.

In conclusion, these results indicate robust intratumoral immune remodeling and a window of tumor-resident T cell expansion following radiation that may be leveraged for the rational design of combinatorial strategies.

Reference

Chow J, Hoffend NC, Abrams SI et al. Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients. Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23721-23729. doi: 10.1073/pnas.2001933117.

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