Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-34676-w |
| _version_ | 1827068318051205120 |
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| author | Laurel B. Darragh Jacob Gadwa Tiffany T. Pham Benjamin Van 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 Von Samedi Mary-Keara Boss Sana D. Karam |
| author_facet | Laurel B. Darragh Jacob Gadwa Tiffany T. Pham Benjamin Van 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 Von Samedi Mary-Keara Boss Sana D. Karam |
| author_sort | Laurel B. Darragh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:54:07Z |
| format | Article |
| id | doaj.art-003c3639bcd64b89a4b408dd9a3666ed |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2025-03-19T23:48:49Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-003c3639bcd64b89a4b408dd9a3666ed2024-10-13T11:25:33ZengNature PortfolioNature Communications2041-17232022-11-0113111810.1038/s41467-022-34676-wElective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumorsLaurel B. Darragh0Jacob Gadwa1Tiffany T. Pham2Benjamin Van Court3Brooke Neupert4Nicholas A. Olimpo5Khoa Nguyen6Diemmy Nguyen7Michael W. Knitz8Maureen Hoen9Sophia Corbo10Molishree Joshi11Yonghua Zhuang12Maria Amann13Xiao-Jing Wang14Steven Dow15Ross M. Kedl16Von Samedi17Mary-Keara Boss18Sana D. Karam19Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Otolaryngology Head and Neck Surgery, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Pathology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Pharmacology, University of Colorado Denver at Anschutz Medical campusDepartment of Pediatrics, Cancer Center Biostatistics Core, University of Colorado Anschutz Medical campusRoche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development (pRED) SchlierenDepartment of Pathology and Laboratory Medicine, University of California Davis, School of MedicineDepartment of Radiation Oncology, Colorado State University, Fort Collins, Colorado. CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusDepartment of Pathology, University of Colorado Denver at Anschutz Medical CampusDepartment of Radiation Oncology, Colorado State University, Fort Collins, Colorado. CampusDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical CampusAbstract 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.https://doi.org/10.1038/s41467-022-34676-w |
| spellingShingle | Laurel B. Darragh Jacob Gadwa Tiffany T. Pham Benjamin Van 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 Von Samedi Mary-Keara Boss Sana D. Karam Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors Nature Communications |
| title | Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors |
| title_full | Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors |
| title_fullStr | Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors |
| title_full_unstemmed | Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors |
| title_short | Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors |
| title_sort | elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors |
| url | https://doi.org/10.1038/s41467-022-34676-w |
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