Immunization of CD200R1KO mice post surgical resection of EMT6 breast cancer leads to long-term (>1year) cure of metastatic tumor growth (TUM2P.1022)

Abstract

Abstract Attenuated expression of CD200 decreases local tumor growth and metastasis in immunocompetent animals. We explored the ability to cure BALB/c CD200KO or CD200R1KO mice of tumors ≤1cm3 in size by surgical resection of localized tumor, followed by immunization with irradiated EMT6 cells using Monophosphoryl Lipid A (MPLA:25υg/mouse) as adjuvant. Controls developed pulmonary and liver metastases within 30 days of surgery. Protection was seen in both CD200KO or CD200R1KO mice, with no macroscopic lung/liver metastases observed in CD200R1KO mice at day 300. After resection and immunization, draining lymph nodes from controls contained tumor cells cloned at limiting dilution in vitro before pulmonary and hepatic metastasis was seen. Within the limits of detection of the assay used (sensitivity ~1 in 107 cells) no tumor cells were detected in CD200R1KO mice, and reductions were seen in CD200KO mice. Infusion of anti-CD8 mAb into surgically treated and immunized CD200R1KO mice attenuated protection from both macroscopic (liver/lung) and microscopic (assayed by limiting dilution of DLN) metastasis. Adoptive transfer of lymphocytes from treated CD200R1KO mice to surgically-treated control mice, particularly after Treg depletion attenuated metastatic growth of tumor, an effect abolished by pretreatment with anti-CD8 mAb. We suggest CD200:CD200R attenuates a potentially tumor-protective CD8 host response to breast cancer following immunotherapy using MPLA as adjuvant.