Researchers at the UCLA David Geffen School of Medicine have proposed that T cell tumor infiltration and the anti-tumor activity of anti-PD-1/PD-L1-based immunotherapy to be modulated through kinase PAK4 activity.
The p21-activated kinase 4 (PAK4) is a member of the PAK family of serine/threonine kinases, which are important effectors of Rho family GTPases and are involved in the regulation of cell morphology and motility via modulation of the actin cytoskeleton. Growing evidences have also implicated PAK4 in oncogenic pathways including anchorage-independent growth, and protection of cells against apoptotic cell death. Although PAK4 is expressed at low levels in most adult tissues, it is highly overexpressed in tumor cell lines and in primary tumors, making it an attractive candidate for developing treatment for different types of cancer.
Researchers at UCLA have discovered the connection between the kinase activity of PAK4 and T cell infiltration in tumors, and proposed novel approaches to facilitate T cell infiltration of tumors and to increase the anti-tumor activity of immunotherapy by modulating the PAK4 activity.