Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

Laurel B. Darragh, Jacob Gadwa, Tiffany T. Pham, Benjamin Court, Brooke Neupert, Nicholas A. Olimpo, Khoa Nguyen, Diemmy Nguyen, Michael W. Knitz, Maureen Hoen, Sophia Corbo, Molishree Joshi, Yonghua Zhuang, Maria Amann, Xiao-Jing Wang, Steven Dow, Ross M. Kedl, Samedi Von, Mary-Keara Boss and Sana D. Karam ()
Additional contact information
Laurel B. Darragh: University of Colorado Denver at Anschutz Medical Campus
Jacob Gadwa: University of Colorado Denver at Anschutz Medical Campus
Tiffany T. Pham: University of Colorado Denver at Anschutz Medical Campus
Benjamin Court: University of Colorado Denver at Anschutz Medical Campus
Brooke Neupert: University of Colorado Denver at Anschutz Medical Campus
Nicholas A. Olimpo: University of Colorado Denver at Anschutz Medical Campus
Khoa Nguyen: University of Colorado Denver at Anschutz Medical Campus
Diemmy Nguyen: University of Colorado Denver at Anschutz Medical Campus
Michael W. Knitz: University of Colorado Denver at Anschutz Medical Campus
Maureen Hoen: University of Colorado Denver at Anschutz Medical Campus
Sophia Corbo: University of Colorado Denver at Anschutz Medical Campus
Molishree Joshi: University of Colorado Denver at Anschutz Medical campus
Yonghua Zhuang: University of Colorado Anschutz Medical campus
Maria Amann: Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development (pRED) Schlieren
Xiao-Jing Wang: University of California Davis, School of Medicine
Steven Dow: Colorado State University, Fort Collins, Colorado. Campus
Ross M. Kedl: University of Colorado Denver at Anschutz Medical Campus
Samedi Von: University of Colorado Denver at Anschutz Medical Campus
Mary-Keara Boss: Colorado State University, Fort Collins, Colorado. Campus
Sana D. Karam: University of Colorado Denver at Anschutz Medical Campus

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radio-sensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies. We find that ENI increases local, distant, and metastatic tumor growth. Multi-compartmental analysis of the primary/distant tumor, the DLNs, and the blood shows that ENI decreases the immune response systemically. Additionally, we find that ENI decreases antigen-specific T cells and epitope spreading. Treating the primary tumor with radiation and immunotherapy, however, fails to reduce regional recurrence, but this is reversed by either concurrent sentinel lymph node resection or irradiation. Our data support using lymphatic sparing radiation therapy for head and neck cancer.

Date: 2022
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DOI: 10.1038/s41467-022-34676-w

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