Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Newton JM

PROVIDER: S-EPMC5823899 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Newton Jared M JM Flores-Arredondo Jose H JH Suki Sarah S Ware Matthew J MJ Krzykawska-Serda Martyna M Agha Mahdi M Law Justin J JJ Sikora Andrew G AG Curley Steven A SA Corr Stuart J SJ

Scientific reports 20180222 1

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 ...[more]

PMID: 29472563

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Project description:Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function and cortisol production. Although recently determined to be monoclonal, very little is known about the mechanisms regulating the development of pituitary hyperplasia and neoplasia in humans. Surgical resection is the treatment of choice for most symptomatic pituitary adenomas. The goal of surgery is the complete removal of the tumor and the success of surgery is strongly affected by the presence of local invasion. However, complete tumor removal is unlikely when there is extensive local invasion. Identifying genes that control the invasiveness and recurrence of this class of tumors will provide therapeutic targets for this class of tumors. We will determine the expression pattern of genes in recurrent and invasive and pituitary adenomas and compare those to non-invasive and non-recurrent tumors. We hypothesize that the differential expression and activation of a number of genes affect pituitary adenoma recurrence and invasiveness. Rationale: Preliminary result showed a differential expression of novel PKC isozymes in non-invasive and invasive pituitary adenomas. PMA, an activator of both novel and classical PKC isozymes increased the expression of gelatinase A (MMP-2) mRNA in human pituitary adenoma cell line. This result raises a fundamental question as to the functional role of novel PKC isozymes and proteases in the invasive phenotype of pituitary adenomas. The primary component of this Specific Aim is to determine whether specific genes are differentially expressed in recurrent or invasive adenomas when compared with control non-invasive tumors. Tissue specimens from non-invasive and invasive (dural invasion based microscopic examination) and recurrent vs non-recurrent tumors will be used for microarray analysis. Frozen pituitaryspecimens will be collected and total RNA extracted with TriZol reagent. We will provide total RNA (10 ug) from non-invasive, invasive, reoccurred and non-occurrent pituitary adenomas.

Dataset Information

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

Publications

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

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