PD-1 and CTLA-4 immunotherapies have been successful in treating some types of cancers but not others. These therapies target molecules on one immune cell type - T cells - to activate dysfunctional T cells that are suppressed by tumors. Nevertheless, other types of immune cells, in particular myeloid cells, are present around the tumors in much larger numbers than T cells. The roles of these myeloid cells in cancer development are not well defined. A better understanding of the function of these myeloid cells in cancer immunology will support development of novel therapeutic strategies for cancer treatment.

We found that LILRB3, a protein present on the surface of human myeloid cells supp...

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PD-1 and CTLA-4 immunotherapies have been successful in treating some types of cancers but not others. These therapies target molecules on one immune cell type - T cells - to activate dysfunctional T cells that are suppressed by tumors. Nevertheless, other types of immune cells, in particular myeloid cells, are present around the tumors in much larger numbers than T cells. The roles of these myeloid cells in cancer development are not well defined. A better understanding of the function of these myeloid cells in cancer immunology will support development of novel therapeutic strategies for cancer treatment.

We found that LILRB3, a protein present on the surface of human myeloid cells supports cancer development. Importantly, we developed anti-LILRB3 blocking antibodies that efficiently inhibit the function of LILRB3 in myeloid cells. We aim to study whether our anti-LILRB3 antibodies can efficiently treat cancers. First, we will determine the function of LILRB3 in control of the activity of tumor-supportive myeloid cells and in cancer development. We will then determine whether LILRB3 interaction with other molecules on the surface of myeloid cells regulates cancer development. Finally, we will dissect how LILRB3 transmit signaling inside the tumor-supportive myeloid cells.

The proposed research is conceptually and technically innovative, based on a series of unique and new tools that will allow us to study the functions of human myeloid cells and their roles in cancer development. Results of this study will open a new research front to study cancer immunology and lead to the development of innovative strategies for cancer treatment based on targeting LILRB3.

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