TY - JOUR
T1 - Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response
AU - Newton, Jared M.
AU - Flores-Arredondo, Jose H.
AU - Suki, Sarah
AU - Ware, Matthew J.
AU - Krzykawska-Serda, Martyna
AU - Agha, Mahdi
AU - Law, Justin J.
AU - Sikora, Andrew G.
AU - Curley, Steven A.
AU - Corr, Stuart J.
N1 - Funding Information:
JMN acknowledges financial support from the National Institute of General Medical Sciences T32 predoctoral training grant (T32GM088129) and the National Institute of Dental & Craniofacial Research F31 NRSA training grant (F31DE026682) both of the National Institutes of Health. This content is soley the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SAC, SJC, MKS and MJW acknowledge the financial support from Kanzius Cancer Research Foundation. We further acknowledge the Cytometry and Cell Sorting Core facility at Baylor College of Medicine with funding from NIH (P30 A1036211, P30 CA125123, and S10 RR024 574) and the expert assistance of Joel M. Sederstrom.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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- A nd 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.
AB - 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- A nd 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.
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U2 - 10.1038/s41598-018-21719-w
DO - 10.1038/s41598-018-21719-w
M3 - Article
C2 - 29472563
AN - SCOPUS:85042548419
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 3474
ER -