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Adoptive immunotherapy of breast cancer with lymph node cells primed by cryoablation of the primary tumor
Authors:Sabel Michael S  Arora Alisha  Su Gang  Chang Alfred E
Institution:University of Michigan, Department of Surgery, Division of Surgical Oncology, 3304 Cancer Center, 1500 East Medical Center, Ann Arbor, MI 48109-0932, USA. msabel@umich.edu
Abstract:Cryoablation of cancer leaves tumor-associated antigens intact in an inflammatory microenvironment that can stimulate a regional anti-tumor immune response. We examined whether cryoablated tumor draining lymph nodes (CTDLN) as adoptive immunotherapy may be an effective immunotherapeutic approach in the adjuvant treatment of breast cancer. BALB/c mice with MT-901 mammary adenocarcinoma tumors underwent cryoablation, resection or no treatment and tumor draining lymph nodes were harvested. Cryoablation resulted in only a mild increase in the absolute number of T-cells but a significant increase in the fraction of tumor-specific T-cells as evidenced on IFN-gamma release assay. FACS analysis demonstrated no significant relative shift in the proportion of CD4(+) or CD8(+) cells. The adoptive transfer of CTDLN resulted in a significant reduction of pulmonary metastases as compared to TDLN from either tumor-bearing mice or mice who underwent surgical excision. Cryoablation prior to surgical resection of breast cancer can be used as a method to generate effector T-cells for adjuvant adoptive cellular immunotherapy.
Keywords:Cryoablation  Breast cancer  Adoptive immunotherapy
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