Highlights in Cancer Research: January 2023

Smokers are at a higher risk for lung cancer development. However, whether and how ultrafine particles generated by incomplete combustion of organic matter from tobacco, or other sources (e.g., industrial pollution, wildfire, etc.), impact the development and progression of lung cancer remained unclear. In this Science Advances paper, Chang et al. examined the impact of ultrafine nano-sized carbon black (nCB) particles, typically seen in a heavy smoker’s lungs, in two models of lung cancer. They discovered that nCB particles accumulate in alveolar macrophages, altering their cellular metabolism that disables the host’s natural defense against tumors. The biochemical properties of nCB allowed their easy access across macrophage’s cellular lipid bilayer membrane and enter mitochondria. nCB rewired macrophages’ mitochondrial metabolism evidenced by increased glycolysis and higher lactate levels. Increased lactate induced higher PDL-1 expression and immunosuppressive proteins (e.g., Interleukin-10 and arginase) in macrophages that promoted tumor growth and metastasis. Notably, mitochondrial dysfunction and increased glycolytic activity in response to nCB were independent of the tumor, indicating that critical immunosuppressive pathways are driven by macrophages. Adoptive transfer of macrophages carrying nCB fueled lung inflammation and exacerbated lung cancer, supporting how nCB alters the host’s responses allowing cancer cells to evade antitumor immunity.