Memorial Sloan-Kettering Cancer Center
The directors of the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford and the Ludwig Center at Memorial Sloan-Kettering Cancer Center are collaborating to investigate the subsets of mouse and human dendritic cells (DC) that express Sirp-α, the receptor for cell surface CD47. The laboratories of Dr. Weissman and Ravindra Majeti, MD, assistant professor of medicine (hematology) have shown that all cancer stem cells tested so far have high levels of CD47, the “don’t eat me” signal for macrophages that are Sirp-α positive. The antibodies that block CD47 have eliminated human acute leukemias and lymphomas that were transplanted to immune-deficient mice. These mice lack cells of the immune system, such as T cells, that are brought into the immune response by DCs. This research should test the hypothesis that CD47 is an “invisibility cloak” for cancer cells to prevent macrophages of the innate immune system and T cells of the adaptive immune system to remove cancers. The collaboration begins with evaluating mouse tumors that are potentially immunogenic by treating the mice with anti-mouse CD47 and testing to learn whether the tumors regress and whether the treated mice have evidence of T-cell stimulation beyond that elicited by the tumors alone. If stimulation occurs, the role of DCs in that stimulation will be tested.