Presentation description
Choroid Plexus Carcinoma (CPC) is a rare malignant brain tumor that typically occurs in children. This tumor arises from malignantly transformed choroid plexus cells, which are the cells within the cerebral ventricles that produce cerebrospinal fluid. CPCs are highly aggressive, with 40% of affected children succumbing to the tumor. The inhibition of macrophage phagocytosis of tumors has recently been implicated as a critical mechanism by which tumors escape immune surveillance. To escape macrophage phagocytosis, tumors express proteins on their cell surface that impart a "don't eat me signal" to the macrophages. The most potent "don't eat me" signal is CD47, which is expressed on every tumor analyzed, including CPCs. However, our laboratory recently determined that a monoclonal antibody that blocks the CD47 "don't eat me" signal (anti-CD47), which promotes significant macrophage tumor cell phagocytosis in most cancers, had minimal to no ability to enhance macrophage phagocytosis of CPC cells from humans and mice. There are other anti-phagocytosis signals, including CD24, PDL1, and Class I MHC, which primarily contribute additional suppression to the dominant CD47 signal. Thus, we hypothesized that these other 'don't eat me' regulators are expressed in CPC. We analyzed three human CPC cell lines by flow cytometry for the expression of CD47 and the previously mentioned 'don't eat me' signals. We determined that tumor cell surface expression of CD24 and CD47 were significantly higher than any of the other don't eat me signals. Furthermore, blocking monoclonal antibodies to CD24 (anti-CD24) promoted macrophage phagocytosis of CPC cells in vitro as effectively as anti-CD47. Furthermore, combining anti-CD24 with anti-CD47 had additional effects beyond either antibody alone. Anti-CD47 combined with monoclonal antibody blockade of any if the other don’t eat me cell surface proteins did not demonstrate any additional phagocytosis beyond anti-CD47 alone. In conclusion, we provided evidence that CD24 and CD47 are dominant don't eat me signals in CPC. We will direct future studies to verify these finding’s in more human CPC patient-derived cell lines and confirm our findings in the in vivo setting. If validated, these studies will provide pre-clinical justification for combining anti-CD24 and anti-CD47 in CPC patients.
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