Role of lymphatic endothelial cells as antigen presenting cells in tumor T cell immunity

During tumor development, the tumor microenvironment impacts negatively anti-tumor T cell responses. Indeed tumors develop mechanisms to avoid immunosurveillance by inducing poorly immunogenic tumors or by setting up tolerogenic mechanisms to inhibit effective immune responses. In the context of lymphangiogenic tumors, lymphatic endothelial cells (LECs) substantially expand in the tumor itself and in the tumor draining lymph node, resulting in increased lymphatic drainage, tumor cell dissemination and metastasis. Recently, LECs have been given much attention as putative unconventional antigen presenting cells. Our group and others have studied their immunoregulatory role, pointing out their contribution in adaptive immunity. Previous studies have demonstrated that LECs can directly present tumor-derived antigens to tumor-specific CD8+ T cells leading to their deletion. However, it is unknown whether LECs can directly present tumor antigens to CD4+ T cells. Using a murine tumor cell line that promotes lymphangiogenesis, we show that, when MHCII expression is abrogated in LEC, tumor growth is reduced, effector T cell functions are enhanced, whereas the phenotype of suppressive regulatory T cells seems to be impaired. These results suggest that tumor-associated LECs would function as tolerogenic antigen-presenting cells, a property that could be blocked to improve immunotherapies in cancer. Further experiments will be performed in order to confirm these results, and extend to a mouse model of non-small cell lung cancer which is initiated by transformation of normal cells and is more physiologically relevant to humans.