RT Journal Article
SR Electronic
T1 Cyclophosphamide Unmasks an Antimetastatic Effect of Local Tumor Cryoablation
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 596
OP 601
DO 10.1124/jpet.109.152603
VO 330
IS 2
A1 Moshe Yair Levy
A1 Abhinav Sidana
A1 Wasim H. Chowdhury
A1 Steven B. Solomon
A1 Charles G. Drake
A1 Ronald Rodriguez
A1 Ephraim J. Fuchs
YR 2009
UL http://jpet.aspetjournals.org/content/330/2/596.abstract
AB Cryoablation of a solitary tumor mass releases intact tumor antigens and can induce protective antitumor immunity but has limited efficacy in the treatment of established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug, selectively depletes regulatory T cells (Tregs) and attenuates suppression of antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to investigate the systemic antitumor effects of in situ cryotherapy alone or in combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was significantly more effective than either surgical excision or cautery at inducing systemic antitumor immunity, resulting in the cure of a fraction of animals with established metastatic disease and resistance to tumor rechallenge. Lymphocytes from cured animals contained an expanded population of tumor-specific, interferon-γ producing T cells and transferred antitumor immunity to naive recipients. Depletion of CD8+ cells significantly impaired the adoptive transfer of antitumor immunity. Furthermore, treatment with Cy and cryoablation was associated with a significant decrease in the ratio of regulatory to effector CD4+ T cells. The combination of tumor cryoablation and Cy induces potent, systemic antitumor immunity in animals with established metastatic disease. The American Society for Pharmacology and Experimental Therapeutics