Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response

• Published in: Scientific reports Vol. 8; no. 1; pp. 3474 - 9
• Main Authors: Newton, Jared M., Flores-Arredondo, Jose H., Suki, Sarah, Ware, Matthew J., Krzykawska-Serda, Martyna, Agha, Mahdi, Law, Justin J., Sikora, Andrew G., Curley, Steven A., Corr, Stuart J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-02-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/21; 13/31; 13/51; 14; 14/1; 14/34; 59; 631/250; 631/67; 639/166; 64; Animal models; Animals; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Cancer; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - radiation effects; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - radiation effects; Chemokines; Cytokines; Cytokines - blood; Female; Humanities and Social Sciences; Humans; Hyperthermia; Hyperthermia, Induced; Immunomodulation; Immunosuppressive agents; Inflammation; Localization; Lymphocytes; Lymphocytes T; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - radiotherapy; Mice; multidisciplinary; Perfusion; Radiofrequency Therapy; Science; Science (multidisciplinary); Solid tumors; T-Lymphocytes - immunology; T-Lymphocytes - radiation effects; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-21719-w

Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response. More specifically we show that multi- and singlet-dose RFT promote an increase in tumor volume in immune competent Balb/c mice, which does not occur in athymic nude models. Further leukocyte subset analysis at 24, 48, and 120 hours after a single RFT show a rapid increase in tumoral trafficking of CD4+ and CD8+ T-cells 24 hours post-treatment. Additional serum cytokine analysis reveals an increase in numerous pro-inflammatory cytokines and chemokines associated with enhanced T-cell trafficking. Overall, these data demonstrate that non-invasive RFT could be an effective immunomodulatory strategy in solid tumors, especially for enhancing the tumoral trafficking of lymphocytes, which is currently a major hindrance of numerous cancer immunotherapeutic strategies.