Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment
Open accessAbstract
Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.
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Radiotherapy promotes the activation of T cells directed against tumor antigens.
“Radiotherapy promotes the activation of T cells directed against tumor antigens12–15.”
From Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation (2021) · cites this paper as [15]
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- Authors
- Lee, Y., Auh, S. L., Wang, Y., Burnette, B., Wang, Y., Meng, Y., Beckett, M., Sharma, R., Chin, R., Tu, T., Weichselbaum, R. R., & Fu, Y.-X.
- Affiliations
- Department of Pathology,
- Department of Radiation and Cellular Oncology/Ludwig Center for Metastasis Research, and
- University of Chicago (US)
- Corresponding author
- Lee, Youjin
- Auh, Sogyong L.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-07-16
- Volume
- 114
- Issue
- 3
- Pages
- 589-595
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2713472
- OpenAlex
- W1999020268
- Cited by
- 1,324
- References
- 29
- Citations by year
- 2026: 29 · 2025: 50 · 2024: 71 · 2023: 88 · 2022: 105 · 2021: 120 · 2020: 147 · 2019: 108 · 2018: 117 · 2017: 104 · 2016: 82 · 2015: 82 · 2014: 77 · 2013: 58 · 2012: 33
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA111423, CA 115540, CA97296, R01CA115540, R01CA111423, P01CA097296)
- National Institute of General Medical Sciences (T32GM007281)
- National Institute of Allergy and Infectious Diseases (R01AI062026, AI 062026)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- ablative radiotherapy, CD8+ T cells, antitumor immunity, T cell priming, fractionated radiotherapy, adjuvant chemotherapy, local immunotherapy, tumor recurrence, metastasis, treatment resistance, cancer immunotherapy
- MeSH terms
- Animals, Combined Modality Therapy, Neoplasms, Experimental, Radiotherapy, Chemotherapy, Adjuvant, Antigen Presentation, CD8-Positive T-Lymphocytes, Tumor Burden, Mice
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