Local Radiation Therapy of B16 Melanoma Tumors Increases the Generation of Tumor Antigen-Specific Effector Cells That Traffic to the Tumor
- 15 June 2005
- journal article
- research article
- Published by The American Association of Immunologists
- Vol. 174 (12), 7516-7523
- https://doi.org/10.4049/jimmunol.174.12.7516
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- Cancer and the chemokine networkNature Reviews Cancer, 2004
- Direct injection of immature dendritic cells into irradiated tumor induces efficient antitumor immunityInternational Journal of Cancer, 2004
- Targeting tumor cells by enhancing radiation sensitivityGenes, Chromosomes and Cancer, 2003
- Myeloma and the newly diagnosed patient: A focus on treatment and managementSeminars in Oncology, 2002
- Tumours can act as adjuvants for humoral immunityImmunology, 2001
- Combining radiation therapy with interleukin-3 gene immunotherapyCancer Gene Therapy, 2000
- Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 MelanomaThe Journal of Experimental Medicine, 1997
- Anti-tumor effects of local irradiation in combination with peritumoral administration of low doses of recombinant interleukin-2 (rIL-2)Radiation Oncology Investigations, 1997
- Effect of Irradiation on Cytokine Production, MHC Antigen Expression, and Vaccine Potential of Interleukin-2 and Interferon-γ Gene-Modified Melanoma CellsCellular Immunology, 1996
- Histological Analysis of Lymphocyte Subsets Infiltrated into Mouse Tumor Tissue Exposed to Local IrradiationOncology, 1987