Endoglin (Cd105) Overexpression is Associated With an Immunosuppressive Tumor Microenvironment

The tumor microenvironment (TME) is one of the major determinants of tumor response to different therapies, especially immunotherapy. tumors with high CD8 + T-cell infiltration that respond well to immunotherapy are called hot tumors, while cold tumors are those with an immunosuppressive microenvironment that respond less well to therapy. Endoglin (CD105) plays a critical role in angiogenesis and its overexpression has been associated with poorer prognosis in various types of cancer. This study aimed to investigate whether high endoglin levels are associated to a cold microenvironment in tumors. Transgenic mice ubiquitously overexpressing endoglin (ENG+) and wild-type C57BL/6J mice (WT) were used to analyse the TME in a Lewis Lung Carcinoma (LLC) subcutaneous xenograft model and in a lung cancer model. The results show that tumors developed in ENG + mice have increased hypoxia, lower infiltration of CD8 + T cells and a higher presence of immunosuppressive cells such as M2 TAMs and Treg, compared to WT mice. This allows us to categorize them as cold tumors. In addition, the analysis of the TME and endoglin expression in human lung adenocarcinoma samples show that cold tumors have higher endoglin levels than hot tumors. These findings suggest that the hypoxic and immunosuppressive microenvironment could be involved in the worse prognosis of tumors with high levels of this protein. This study highlights the potential of endoglin as a marker to predict the response to immunotherapy and guide personalized treatment strategies in cancer patients.