Adoptive immunotherapy of breast cancer with lymph node cells primed by cryoablation of the primary tumor.
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.
Sabel
Michael S
MS
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
Arora
Alisha
A
Su
Gang
G
Chang
Alfred E
AE
D000230:Adenocarcinoma / Q000276:immunology / Q000601:surgery / Q000628:therapy; D000818:Animals; D003131:Combined Modality Therapy; D003452:Cryosurgery; D005260:Female; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology
D007371:Interferon-gamma