Cryoablation and Meriva have strong therapeutic effect on triple-negative breast cancer

Abstract

Keywords: adjuvant, cryoablation, immunogenic tumor cell death, Mage-b, Meriva, metastatic breast cancer, Survivin, triple-negative breast cancer, vaccinesInterleukin-6, a cytokine produced particularly by triple-negative breast cancers, strongly inhibits T cell responses in the tumor microenvironment. Here we tested cryoablation combined with Meriva (a lecithin delivery system of curcumin with improved bioavailability) in mice with metastatic breast cancer (4T1). Cryoablation involves killing of tumor cells through freezing and thawing, resulting in recruitment of tumor-specific T cells, while curcumin stimulates T cells through the reduction of IL-6 in the TME. Cryoablation plus Meriva accumulated and activated CD8C T cells to multiple tumor-associated antigens such as Mage-b and Survivin (both expressed by 4T1 tumors). This correlated with a nearly complete reduction of 4T1 primary tumors and lung metastases while little effect was observed from saline or Meriva alone (28 d after tumor cell injection). The survival rate in the group of cryoablation plus Meriva was significantly improved compared to all control groups. Using a less aggressive 4T1 model expressing luciferase (4T1.2luc3), we demonstrated that all mice receiving saline or Meriva developed metastases in the lungs and a primary tumor (38 d after tumor cell injection; and died soon after that), but not the mice receiving cryoablation or cryoablation plus Meriva. However, on day 58 the mice receiving cryoablation developed 4T1.2luc3 metastases in the lungs, while mice receiving cryoablation plus Meriva were free of metastases. These results strongly suggest that cryoablation delayed the development of lung metastases on the short-term, but Meriva administered after cryoablation was significantly better in delaying the development of lung metastases and survival on the long-term.

A Phase 2 Study to Assess the Immunomodulatory Capacity of a Lecithin-based Delivery System of Curcumin in Endometrial Cancer

“…Several studies have observed changes in inflammatory biomarkers upon curcumin intake. The absence of changes in inflammatory biomarker levels seems contradictory to other studies where CP treatment has shown to decrease the levels of several inflammatory markers such as CRP (25), IL-1β (41), IL-6 (8, 41, 42), IL-22 (43), sCD40L (41). However, in our study, the levels of a substantial number of analytes were below the detection limit, so further decreases cannot be detected.…”

“…Curcumin has been shown to inhibit the accumulation of myeloid-derived suppressor cells (MDSC) and their interaction with cancer cells and induces the differentiation/maturation of MDSC (7). Curcumin reduced intratumoral IL-6 production and metastasis formation in a breast cancer model and, when combined with cryoablation, induced robust anti-tumor T cell immunity and reduced tumor growth (8). In RAW 264.7 murine macrophages, a curcumin formulation significantly decreased the LPS-induced pro-inflammatory mediators NO, PGE 2 , and IL-6 by inhibiting activation of NF-κB (9).…”

Integrative Medicine in Interventional Oncology: A Virtuous Alliance

“…For example, curcumin has been used for millennia because it improves immunity against cancer. Interestingly, experimental studies in mice have demonstrated significant inhibition of tumor growth after combining curcumin with percutaneous cryoablation [20]. These results are supported by several preclinical and clinical studies demonstrating that percutaneous ablations combined with appropriate immunomodulators can induce a therapeutically effective systemic anti-tumor immune response [21].…”

<p>Cryoablation In The Management Of Breast Cancer: Evidence To Date</p>

“…More importantly, it is a repeatable procedure in case of local relapse or incomplete ablation. Furthermore, it does not interrupt other systemic therapies, ie, systemic treatment for metastatic disease, and can act in synergy with them 1,19,20. Cryoablation is not without possible adverse effects.…”