Immunization of CD200R1KO mice post surgical resection of EMT6 breast cancer leads to long-term (>1year) cure of metastatic tumor growth (TUM7P.921)

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 along with CpG as adjuvant. Control animals 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 on sacrifice at day 300. After resection and immunization, draining lymph nodes from controls contained tumor cells cloned at limiting dilution in vitro even 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 at limiting dilution in similarly treated CD200R1KO mice, and significant reductions were seen in CD200KO mice. Infusion of anti-CD4, but less so 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 also attenuated metastatic growth of tumor, which was abolished by pretreatment of transferred cells with anti-CD4 mAb. Our data suggest CD200:CD200R attenuates a potentially tumor-protective CD4 host response to breast cancer.