Advancing lung cancer therapy - leveraging cell biology to improve immunotherapy and anti-angiogenic strategies.

The standard of care for lung cancer typically involves a multidisciplinary approach including surgery, chemotherapy, radiotherapy, targeted therapy and immunotherapy, with treatment strategies tailored to the cancer subtype, disease stage and patient condition. Despite these efforts, the overall 5-year relative survival rate remains low, at ∼27%, with outcomes varying significantly by stage at diagnosis. These limited survival rates highlight the urgent need for more effective therapeutic strategies and innovative treatment approaches. A combination therapy involving immune checkpoint inhibitors and anti-angiogenic drugs has emerged as a promising strategy for lung cancer treatment. However, challenges such as low response rates and acquired resistance continue to hinder the success of this approach. The tumour microenvironment, particularly the intricate molecular and cellular interactions between immune cells and endothelial cells, plays a pivotal role in determining the efficacy of and resistance to therapeutic strategies. In this Perspective, we discuss the interplay between cancer cells and immune and vascular cells, highlighting how a detailed understanding of the cell biology of the tumour microenvironment might advance current therapies. Additionally, we describe alternative vascular modulation approaches that could potentially improve the effectiveness of immune checkpoint inhibitors in lung cancer treatment.