VHL loss is common in clear cell renal cell carcinoma (ccRCC) and triggers a pseudohypoxic state in mutated cells. A study by Jeffrey Rathmell and colleagues now suggests that Vhl deletion also affects the tumour immune-cell infiltrate in RCC.

The myeloid cells that infiltrated Vhl−/− tumours were also functionally distinct from those in control tumours, as they were more phagocytic ex vivo and had enhanced expression of inflammatory genes and surface markers (including CD11c). Metabolically, Vhl−/− tumours had higher glucose uptake than controls, and this difference was mainly driven by myeloid cells. Increased expression of CX3C-chemokine ligand 1 (CX3CL1) might be a key alteration in Vhl−/− cells that drives myeloid cell recruitment, as knocking out Cx3cl1 in these cells reduced the numbers of myeloid cells and their expression of CD11c.