Environmental pollutants and age-related hematopoietic changes are critical drivers of cancer initiation and progression, particularly in lung cancer. This review synthesizes findings from two pivotal studies highlighting their impact, with a focus on EGFR-driven lung cancer.
Exposure to particulate matter (PM2.5), a major environmental pollutant, has been strongly linked to increased lung cancer incidence, especially in EGFR-driven cases prevalent among never-smokers and light smokers. A study of 32,957 patients revealed that PM2.5 exposure induces inflammation through macrophage recruitment and the release of interleukin-1β. This inflammatory response drives EGFR-mutant lung cells into a progenitor-like state, fostering tumorigenesis by sustaining tumor-propagating cell populations. These findings underscore the potential for reducing PM2.5 exposure to alleviate disease burden, particularly in vulnerable populations.
Clonal hematopoiesis of indeterminate potential (CHIP) and tumor-infiltrating clonal hematopoiesis (TI-CH) have emerged as significant contributors to cancer progression. In a cohort of 421 early-stage non-small cell lung cancer (NSCLC) patients, 42% exhibited TI-CH, which was associated with higher recurrence and mortality rates. Mutations in the TET2 gene, common in CHIP, were shown to enhance myeloid cell migration, creating a myeloid-rich tumor microenvironment that promotes tumor growth. Preclinical models demonstrated that TET2-mutant myeloid cells accelerate tumor organoid growth, further implicating age-related hematopoietic changes in cancer evolution.
Together, these studies reveal the complex interplay of environmental pollutants and age-related inflammation in lung cancer. They suggest that targeting both environmental exposures, such as PM2.5, and age-related hematopoietic alterations, like CHIP and TI-CH, may provide novel therapeutic avenues to mitigate cancer risk and progression.