Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer

Autor: Nader El-Sayes, Natalie Mercanti, Alyssa Vito, Stephanie M. Rathmann, John F. Valliant, Karen L. Mossman
Rok vydání: 2021
Předmět:
Oncology
medicine.medical_specialty
QH301-705.5
medicine.medical_treatment
Triple Negative Breast Neoplasms
Catalysis
Article
Inorganic Chemistry
Mice
Internal medicine
Cell Line
Tumor
medicine
Tumor Microenvironment
Animals
Humans
Immunologic Factors
Biology (General)
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Immune Checkpoint Inhibitors
Spectroscopy
Triple-negative breast cancer
oncology_oncogenics
business.industry
Organic Chemistry
Cancer
radionuclide therapy
General Medicine
Immunotherapy
medicine.disease
Combined Modality Therapy
Xenograft Model Antitumor Assays
Immune checkpoint
Computer Science Applications
Blockade
immune checkpoint therapy
Clinical trial
Radiation therapy
Chemistry
triple negative breast cancer
Radionuclide therapy
Female
immunotherapy
Neoplasm Recurrence
Local
business
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 9
International Journal of Molecular Sciences, Vol 22, Iss 4843, p 4843 (2021)
ISSN: 1422-0067
Popis: Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low, and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabeled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.
Databáze: OpenAIRE
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