Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells

Abstract

Tumor immunology fundamentals suggest immunological surveillance has the ability to recognize malignant cells and kill them before a tumor develops. However, cancer cells employ evasion mechanisms whereby the immune system may be actively suppressed or even tolerized to the tumor. Recently cancer stem cells were linked to tumor initiation and formation. However, no reports have addressed whether these cells participate in a tumor's ability to evade immune surveillance. Recently the glycoprotein CD200, expressed within the innate immune system and other tissues and cells, was shown to be involved in tolerance. Here we describe CD200 co-expression with stem cell markers found on prostate, breast, brain, and colon cancers. This is the first report describing an immunomodulatory molecule on epithelial cancer stem cells. This important finding suggests a mechanism by which a tumor might evades immune system detection.

Role of CD200 expression in regulation of metastasis of EMT6 tumor cells in mice

“…cells (acting via PD1 to sustain Treg cells) [48]. CD200 is expressed on human breast cancer cells [26], and sCD200 exists in serum of metastatic breast cancer patients (unpublished data).We hypothesize that data from the murine EMT6 model will be relevant to humans.…”

“…Human breast cancer stem cells express CD200, and CD200 ? cells but not CD200 -cells grow in SCID mice to form a tumor [26,27]. CD200 may define subsets of tumor cells with aggressive behavior, which facilitate growth of CD200 -cells.…”

CD200: A putative therapeutic target in cancer

“…A recent study reported the coexpression of CD200 with cancer stem cell markers found on prostate, breast, brain and colon cancers [36]. Given the immunosuppressive role of CD200, overexpression of CD200 in cancer tissues may facilitate an escape from the immune response and provide a mechanism whereby cancer stem cells are able to avoid detection by the immune system and remain as residual disease.…”

CD200-expressing human basal cell carcinoma cells initiate tumor growth

“…Although expression of CD200 and K15 is not regulated by SHH, this does not exclude the possibility that BCC arises from transformed interfollicular or hair follicle differentiated keratinocytes. Putative TICs in multiple cancer cell lines have also been found to express CD200 (44). In human acute myeloid leukemia and multiple myelomas, CD200 expression is associated with poor prognosis (45)(46)(47).…”