Malignant melanoma deploys elegant molecular mechanism to evade immune responses
Immune evasion in cancer is really interesting and particularly important because immune therapy has really emerged as a groundbreaking therapy. But, while immunotherapy excels in blood cancers, it still struggles in  solid tumors. Part of the reason for this is that a solid group of cancer cells can much more easily change their microenvironment to exclude immune cells.<p>So this paper explores one of the ways they do that. Cancer cells turn off a protein that sits on the surface of normal human cells that immune cells regularly bind to. Binding to this protein, CD58, causes changes in the immune cell. What these changes are critically depends on the <i>other</i> signals that the immune cell senses on the surface of the cell. If it senses another (somewhat famous) protein, PD-L1, the immune cell self destructs, as PD-L1’s presence typically means that a cell is normal and healthy. But, cancer cells  frequently evolve to over generate PD-L1, thereby creating an micro-environment filled with self destruct signals. Further, the other protein CD58 actually increases the physical force of immune cell binding, so when cancer cells turn off CD58 they actually get more slippery.<p>This paper explores an interesting connection between the two proteins. There’s a third protein which binds to both of them and increases the amount of time they're active on the cell’s surface. Honestly I haven’t had time to fully digest this bit, but it seems like the regulatory protein preferentially binds to CD58, which is good because it promotes immune cell adhesion and recognition of the tumor cell. But! When CD58 is lost, it then binds to PDL1 and promotes immune cell evasion.<p>Why nature chose this as a regulatory mechanism is kind of baffling, but exactly the kind of thing that makes cell biology interesting