Abstract
CD200 (OX-2) is a cell surface glycoprotein that imparts immune privileges by suppressing alloimmune and autoimmune responses through its receptor, CD200R, expressed primarily on myeloid cells. The ability of CD200 to suppress myeloid cell activation is critical for maintaining normal tissue homeostasis but may also enhance the survival of migratory neoplastic cells. We show that CD200 expression is largely absent in well-differentiated primary squamous cell carcinoma (SCC) of the skin, but is highly induced in SCC metastases to the lymph node and other solid tissues. CD200 does not influence the proliferative or invasive capacity of SCC cells or their ability to reconstitute primary skin tumors. However, loss of CD200 impairs the ability of SCC cells to metastasize and seed secondary tumors, indicating that the survival of CD200(+) SCC cells may depend on their ability to interact with CD200R(+) immune cells. The predominant population of CD200R(+) stromal cells was CD11b(+)Gr-1(+) myeloid-derived suppressor cells, which release elevated levels of granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor when in the presence of SCC cells in a CD200-dependent manner. Collectively, our findings implicate CD200 as a hallmark of SCC metastasis and suggest that the ability of CD200(+) SCC keratinocytes to directly engage and modulate CD200R(+) myeloid-derived suppressor cells is essential to metastatic survival.
Highlights
Solid tumor metastasis is a complex multistep process, during which neoplastic cells must invade tissue, enter and navigate via the circulatory system, and extravasate to colonize a distant foreign tissue [1, 2], and the success of this process is highly dependent on modulating the immune system [3, 4]
No CD200 expression was detected in benign papillomas (0 of 9) or well-differentiated (WD) squamous cell carcinoma (SCC) of the skin (0 of 24); CD200 induction was first observed in the invasive front of poorly differentiated (PD) SCC (Fig. 1A) and CD200 was highly induced in metastatic SCC in the lymph node (14 of 14, 100%) and lung (3 of 3, 100%; Table 1)
These results indicate that induction of CD200 strongly correlates with late stage skin carcinogenesis and raises the possibility that CD200 may play a role in SCC metastasis
Summary
Solid tumor metastasis is a complex multistep process, during which neoplastic cells must invade tissue, enter and navigate via the circulatory system, and extravasate to colonize a distant foreign tissue [1, 2], and the success of this process is highly dependent on modulating the immune system [3, 4]. The immunosuppressive capacity of CD200 is crucial for maintaining homeostasis in a number of tissues, including the central and peripheral nervous system [14], Authors' Affiliations: Departments of 1Pathology and 2Dermatology, Columbia University, College of Physicians and Surgeons, New York, New York. During homeostasis, CD200 maintains an appropriate level of activated macrophages to preserve tissue integrity; whereas during injury-induced heightened inflammatory states, CD200 provides immune privilege to CD200+ tissues to escape macrophage-mediated tissue damage [16, 18]. CD200R, a transmembrane glycoprotein, is expressed mostly in myeloid cells [13, 19] and smaller subsets of lymphoid-derived cells [13, 20]. There are five described CD200R isoforms, CD200R1–R5, of which CD200R1 is reported to be the major mediator of CD200 immunosuppressive signaling [13, 21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
