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

Dinesh Chandra, Arthee Jahangir, Francois Cornelis, Klara Rombauts, Lydie Meheus, Cheryl L. Jorcyk, Claudia Gravekamp

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Interleukin-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 CD8+ 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.

Original languageEnglish (US)
JournalOncoImmunology
Volume5
Issue number1
DOIs
StatePublished - 2016

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Triple Negative Breast Neoplasms
Cryosurgery
Therapeutic Uses
Neoplasm Metastasis
Lung
Neoplasms
T-Lymphocytes
Curcumin
Interleukin-6
Injections
Tumor Microenvironment
Lecithins
Neoplasm Antigens
Luciferases
Freezing
Biological Availability

Keywords

  • Adjuvant
  • Cryoablation
  • Immunogenic tumor cell death
  • Mage-b
  • Meriva
  • Metastatic breast cancer
  • Survivin
  • Triple-negative breast cancer
  • Vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Cryoablation and meriva have strong therapeutic effect on triple-negative breast cancer. / Chandra, Dinesh; Jahangir, Arthee; Cornelis, Francois; Rombauts, Klara; Meheus, Lydie; Jorcyk, Cheryl L.; Gravekamp, Claudia.

In: OncoImmunology, Vol. 5, No. 1, 2016.

Research output: Contribution to journalArticle

Chandra, Dinesh ; Jahangir, Arthee ; Cornelis, Francois ; Rombauts, Klara ; Meheus, Lydie ; Jorcyk, Cheryl L. ; Gravekamp, Claudia. / Cryoablation and meriva have strong therapeutic effect on triple-negative breast cancer. In: OncoImmunology. 2016 ; Vol. 5, No. 1.
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