The vital role of p97/valosin-containing protein-mediated degradation pathways in tumour immunity

p97, also known as valosin-containing protein (VCP), is an evolutionarily conserved ATPase that functions upstream of the two major protein degradation pathways: the ubiquitin-proteasome system (UPS) and autophagy. In this capacity, it plays a central role in maintaining protein homeostasis and genome stability. The roles of the UPS and autophagy in regulating immune responses including within the tumour microenvironment (TME), are well established. However, the contribution of p97 to shaping immune responses in the TME has only recently begun to emerge. Recent findings indicate that p97 not only affects cancer cells directly but also plays a critical role in the heterogeneous TME, acting as a key driver of tumour progression, therapy resistance, and metastatic initiation. In this review, we will discuss the role of the p97 system in tumour immunity. A deeper understanding of how p97 regulates immune responses is essential for advancing cancer biology and oncology.