Local Radiation Therapy of B16 Melanoma Tumors Increases the Generation of Tumor Antigen-Specific Effector Cells That Traffic to the Tumor
Open accessAbstract
Immunotherapy of cancer is attractive because of its potential for specificity and limited side effects. The efficacy of this approach may be improved by providing adjuvant signals and an inflammatory environment for immune cell activation. We evaluated antitumor immune responses in mice after treatment of OVA-expressing B16-F0 tumors with single (15 Gy) or fractionated (5 × 3 Gy) doses of localized ionizing radiation. Irradiated mice had cells with greater capability to present tumor Ags and specific T cells that secreted IFN-γ upon peptide stimulation within tumor-draining lymph nodes than nonirradiated mice. Immune activation in tumor-draining lymph nodes correlated with an increase in the number of CD45+ cells infiltrating single dose irradiated tumors compared with nonirradiated mice. Similarly, irradiated mice had increased numbers of tumor-infiltrating lymphocytes that secreted IFN-γ and lysed tumor cell targets. Peptide-specific IFN-γ responses were directed against both the class I and class II MHC-restricted OVA peptides OVA257–264 and OVA323–339, respectively, as well as the endogenous class I MHC-restricted B16 tumor peptide tyrosinase-related protein 2180–188. Adoptive transfer studies indicated that the increased numbers of tumor Ag-specific immune cells within irradiated tumors were most likely due to enhanced trafficking of these cells to the tumor site. Together these results suggest that localized radiation can increase both the generation of antitumor immune effector cells and their trafficking to the tumor site.
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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.”
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- Authors
- Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger, J. G., & Lord, E. M.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06
- Volume
- 174
- Issue
- 12
- Pages
- 7516-7523
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1524125877
- Cited by
- 966
- References
- 51
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 52 · 2023: 64 · 2022: 73 · 2021: 84 · 2020: 77 · 2019: 70 · 2018: 81 · 2017: 70 · 2016: 53 · 2015: 41 · 2014: 51 · 2013: 40 · 2012: 35
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA28332)
- National Cancer Institute (CA 28332, R01CA028332)
- National Institute of Allergy and Infectious Diseases (AI-07285, T32AI007285)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- local radiotherapy, B16 melanoma, tumor antigen-specific T cells, tumor-infiltrating lymphocytes, tumor-draining lymph nodes, interferon-gamma, antigen presentation, tyrosinase-related protein 2, adoptive transfer, T cell migration, fractionated irradiation, antitumor immunity
- MeSH terms
- Animals, Antigens, Neoplasm, Cell Movement, Cytotoxicity Tests, Immunologic, Dose-Response Relationship, Radiation, Lymph Nodes, Lymphocyte Activation, Melanoma, Experimental, Mice, Inbred A, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, T-Lymphocytes, Cytotoxic, Lymphocytes, Tumor-Infiltrating, Antigen Presentation, Lymphocyte Count, Cell Line, Tumor, Cell Proliferation, Mice
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