Despite the remarkable clinical success of immunotherapies in a subset of cancer patients,
many fail to respond to treatment and exhibit resistance. Here, we found that genetic or
pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and
lysosomal biogenesis, upregulated surface expression of major histocompatibility complex
class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer
cell killing mediated by CD8+ T cells. Genetic depletion or pharmacologic inhibition of …

The widespread success of cancer immunotherapies suggests a promising future-but has
been subverted by unresponsiveness and resistance. Current research has furthered the
understanding of immunotherapy resistance through the findings of “hot”(responsive) and
“cold”(unresponsive) tumors. Here, we focus on the genetic and pharmacological inhibition
of PIKfyve, a lipid kinase regulator of autophagic flux and lysosomal biogenesis. We find that
inhibition of PIKfyve results in the upregulation of major histocompatibility complex class I …