Year: 2024
Type: article
Abstract: Background: The majority of experimental approaches for cancer immunotherapy are tested against relatively small tumors in tumor-bearing mice, because in most cases advanced cancers are resistant to the treatments. In this study, we asked if even late-stage mouse tumors can be eradicated by a rationally designed combined radio-immunotherapy (CRI) regimen. Methods: CRI consisted of local radiotherapy, intratumoral IL-12, slow-release systemic IL-2 and anti- CTLA-4 antibody. Therapeutic effects of CRI against several weakly immunogenic and immunogenic mouse tumors including B78 melanoma, MC38 and CT26 colon carcinomas and 9464D neuroblastoma were evaluated. Immune cell depletion and flow cytometric analysis were performed to determine the mechanisms of the antitumor effects. Results: or larger were eradicated by CRI. Flow analyses of the tumors revealed reduction of T regulatory (Treg) cells and increase of CD8/Treg ratios following CRI. Rapid shrinkage of the treated tumors did not require T cells, whereas T cells were involved in the systemic effect against the distant tumors. Cured mice developed immunological memory. Conclusions: These findings underscore that rationally designed combination immunotherapy regimens can be effective even against large, late-stage tumors.
Source: Frontiers in Immunology
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
Awards: Molecular Targeted Radionuclide Therapy for Tumor Immunomodulation and Enhancing Immunotherapy Response, Head and Neck Cancer SPORE at the University of Wisconsin, Immunomodulation of the Tumor Microenvironment with Molecular Targeted Radiotherapy to Facilitate an Adaptive Anti-Tumor Immune Response to Combined Modality Immunotherapies, Enhancing Antibody-directed Innate Immunity to Improve Cancer Outcome, Combining Radiation and Tumor-specific AntIbody Therapies to Elicit in Situ Tumor Vaccination, Discovery and Development of Optimal Immunotherapeutic Strategies for Childhood Cancers
OpenAlex ID: W4400664940