Lysosome as the Black Hole for Checkpoint Molecules.

Lysosomes, as digestive organelles full of hydrolases, have complex functions and play an important role in cellular physiological and pathological processes. In normal physiological conditions, lysosomes can sense the nutritional state and be responsible for recycling raw materials to provide nutrients, affecting cell signaling pathways and regulating cell proliferation. Lysosomes are related to many diseases and associated with metastasis and drug resistance of tumors. In recent years, much attention has been paid to the tumor immunotherapy especially immune checkpoint blockade therapy. Accumulating data suggest that lysosomes may serve as a major destruction for immune checkpoint molecules, and secretory lysosomes can temporarily store immune checkpoint proteins. Once activated, the compounds contained in secretory lysosomes are released to the surface of cell membrane rapidly. Inhibitions of lysosomes can overcome the chemoresistance of some tumors and enhance the efficacy of immunotherapy.