The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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5. Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer
Chang, C-Y. et al. Science Advances. 8(46). (2022).
doi: 10.1126/sciadv.abq0615.
Summary of the findings
Environmental airborne nCB particles, found in cigarette smoke and other air pollutants, increase tissue inflammation in the lungs. In addition, nCBs are taken in by the alveolar macrophages, damaging the mitochondria and so favouring glycolysis over oxidative phosphorylation. This leads to increased lactate levels in the microenvironment which impairs the proper functioning of the immune system. This on the background of tissue inflammation favours tumour development.
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.
Future impact
Cigarette smoking remains the number one cause of lung cancer worldwide. However, exposure to industrial and environmental air pollution impacts a broader range of the population at risk. This study shows that small airborne particles, nCB, can promote immunosuppression in the lung, demonstrating the importance of environmental pollutants in cancer development. The newly discovered immunometabolic pathways identified in this study play a key role in lung cancer development and progression. Harnessing the molecular mechanisms critical in changing the immune environment in the lungs could be used to provide new treatment options for preventing and or treating lung cancer.
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The Cancer Researcher is an online magazine for the cancer research community from the European Association for Cancer Research.
The EACR, a registered charity, is a global community for those working and studying in cancer research. Our mission is “The advancement of cancer research for the public benefit: from basic research to prevention, treatment and care.”
