Pericyte phenotype switching in cancer

Pericytes play an important physiological role as guardians of vascular integrity. In cancer, however, pericytes undergo profound phenotypic changes which foster tumor progression. Emerging transcriptomics and functional data provide evidence for a shift from quiescent to highly proliferating, matrix-secreting pericytes which destabilize the vasculature and create immune deserts. However, due to their inherent plasticity, proliferative tumor pericytes can be ‘coerced’ to switch back into a more quiescent and contractile state, a process which underpins durable tumor vessel normalization. Therapeutically, pericyte phenotype switching can be induced by targeting oncogenic, metabolic, or microtubule signaling pathways which induce Rho kinase activity. Thus, harnessing pericyte plasticity provides unique opportunities to synergize targeted anticancer therapies with immunotherapy.