Immune modulation by melanoma and ovarian tumor cells through expression of the immunosuppressive molecule CD200.
OBJECTIVE
Immune escape by tumors can occur by multiple mechanisms, each a significant barrier to immunotherapy. We previously demonstrated that upregulation of the immunosuppressive molecule CD200 on chronic lymphocytic leukemia cells inhibits Th1 cytokine production required for an effective cytotoxic T cell response. CD200 expression on human tumor cells in animal models prevents human lymphocytes from rejecting the tumor; treatment with an antagonistic anti-CD200 antibody restored lymphocyte-mediated tumor growth inhibition. The current study evaluated CD200 expression on solid cancers, and its effect on immune response in vitro.


RESULTS
CD200 protein was expressed on the surface of 5/8 ovarian cancer, 2/4 melanoma, 2/2 neuroblastoma and 2/3 renal carcinoma cell lines tested, but CD200 was absent on prostate, lung, breast, astrocytoma, or glioblastoma cell lines. Evaluation of patient samples by immunohistochemistry showed strong, membrane-associated CD200 staining on malignant cells of melanoma (4/4), ovarian cancer (3/3) and clear cell renal cell carcinoma (ccRCC) (2/3), but also on normal ovary and kidney. CD200 expression on melanoma metastases was determined by RT-QPCR, and was found to be significantly higher in jejunum metastases (2/2) and lung metastases (2/6) than in normal samples. Addition of CD200-expressing, but not CD200-negative solid tumor cell lines to mixed lymphocyte reactions downregulated the production of Th1 cytokines. Inclusion of antagonistic anti-CD200 antibody restored Th1 cytokine responses.


CONCLUSIONS
These data suggest that melanoma, ccRCC and ovarian tumor cells can express CD200, thereby potentially suppressing anti-tumor immune responses. CD200 blockade with an antagonistic antibody may permit an effective anti-tumor immune response in these solid tumor types.
Alexion Antibody Technologies, Inc., 3985 Sorrento Valley Blvd, Ste A, San Diego, CA 92121, USA.
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Siva
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Oltean
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Kretz-Rommel
D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000276:immunology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; C042739:antigens, CD200