Markers and vulnerabilities of senescent cells in post-therapy tumors
José Alberto López
Centro de Investigación del Cáncer. Universidad de Salamanca - CSIC
Chemotherapy and other treatments against solid tumors often generate a population of cells which have received a sublethal dose of damage, resulting in the induction of cellular senescence. Senescent cells arrest their cell cycle, although their persistence in the residual tumor after treatment is deleterious, due to the production of chemokines and other soluble factors, and to their complex interplay with the immune system. Senescent cells overexpress immune checkpoint ligands, namely PD-L2 and PD-L1, which exert an inhibitory effect on T cells and other immune cells. PD-L2 ablation in tumor cells results in enhanced tumor control when combined with genotoxic chemotherapy, resulting in increased elimination of senescent cells and altered recruitment of immunosuppressive myeloid cells into the tumor. We aim to further understand the interactions between damaged cells and the host immune system, as well as to develop novel strategies for non-invasive estimation of senescent cell burden in vivo.