Inhibiting C5a/C5aR axis reduces myeloid-derived suppressor cells and enhances PD-1 blockade therapy in lung cancer

In the US (1), and the world, lung cancer remains the leading cause of cancer death. Lung cancer causes more deaths than the next three most common cancers of the colon, breast and prostate combined. In the US an estimated 160,000 Americans and worldwide more than 1.1 million people die from lung cancer annually (2). Approximately 220,000 new cases occur every year in the US. Although previously thought to be non-immunogenic and nonresponsive to immune-based therapies, recent groundbreaking studies in lung cancer with immune checkpoint blockade therapy reveal robust anti-tumor activity and durable responses in previously treated patients with progressive locally advanced or metastatic non-small cell lung cancer (NSCLC). This has also changed the treatment paradigm leading to immune checkpoint blockade as a frontline therapy for advanced stage lung cancer. Studies in NSCLC and melanoma patient-derived tumor specimens reveal that responses to immune checkpoint blockade therapy rely on tumor infiltration of activated T effector cells (3-7).