Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms

Lung cancer, with a high mortality rate, poses challenges in treatment due to its invasiveness and heterogeneity. Lung cancer stem cells (LCSCs) are considered key contributors to recurrence and metastasis because of their self-renewal, pluripotency, and drug resistance. The tumor microenvironment (TME) is intricately intertwined with LCSCs, where cellular factors, hypoxic conditions, and extracellular matrix components within the TME modulate LCSCs' properties through various signaling pathways. This review analyzes the interaction between the TME and LCSCs, elucidates their regulatory mechanisms, and explores potential therapeutic strategies based on these mechanisms, including immunotherapy, anti-angiogenesis therapy, and targeting CAFs and stromal metabolism. We believe that a deeper understanding of the interaction between the TME and LCSCs is crucial for the development of novel therapeutic approaches and may offer more effective treatment options for lung cancer patients.