Hot and Cold Tumors: Is Endoglin (CD105) a Potential Target for Vessel Normalization?

SIMPLE SUMMARY: The prognosis and response to immunotherapy depends largely on the composition of the tumor microenvironment (TME). So-called cold tumors are rich in cells and molecules that inhibit the antitumor response and, therefore, are associated with a worse prognosis. In contrast, hot tumors are rich in antitumor cells and respond well to immunotherapy. The creation of one type of TME or another is highly dependent on angiogenesis, inflammation, and cancer-associated fibroblast (CAF) accumulation. Endoglin (CD105) is a protein involved in these three processes, making it a possible target for the conversion of cold tumors into hot tumors. In this review we summarize the role of endoglin in these processes and present the anti-endoglin therapies already under study that could be applied for vascular normalization. ABSTRACT: Tumors are complex masses formed by malignant but also by normal cells. The interaction between these cells via cytokines, chemokines, growth factors, and enzymes that remodel the extracellular matrix (ECM) constitutes the tumor microenvironment (TME). This TME can be determinant in the prognosis and the response to some treatments such as immunotherapy. Depending on their TME, two types of tumors can be defined: hot tumors, characterized by an immunosupportive TME and a good response to immunotherapy; and cold tumors, which respond poorly to this therapy and are characterized by an immunosuppressive TME. A therapeutic strategy that has been shown to be useful for the conversion of cold tumors into hot tumors is vascular normalization. In this review we propose that endoglin (CD105) may be a useful target of this strategy since it is involved in the three main processes involved in the generation of the TME: angiogenesis, inflammation, and cancer-associated fibroblast (CAF) accumulation. Moreover, the analysis of endoglin expression in tumors, which is already used in the clinic to study the microvascular density and that is associated with worse prognosis, could be used to predict a patient’s response to immunotherapy.