Researchers at have discovered how lung tumors can manipulate the immune system to protect themselves. The study, published in Cancer Immunology Research, helps explain why many patients with non-small cell lung cancer (NSCLC) do not respond well to immunotherapy and points to a possible new treatment target.
The research focuses on regulatory T cells, or Tregs. Normally, these cells prevent the immune system from attacking healthy tissues. But in lung cancer, tumors take advantage of them. Stressed cancer cells release large amounts of ATP. Tregs inside the tumor have high levels of a receptor called P2RX7, which senses this ATP. When activated, P2RX7 causes Tregs to gather in the tumor and block the “killer” immune cells that would normally attack the cancer.
The study found that higher levels of P2RX7 in tumors were linked to worse survival. P2RX7 also helps Tregs produce CTLA-4, a molecule that further suppresses immune responses. When researchers blocked P2RX7 in laboratory models, immune cells worked better with B cells, producing more cancer-targeting antibodies and forming organized immune structures linked to better outcomes.
Although drugs targeting P2RX7 are not yet approved for cancer treatment, the findings suggest that blocking this receptor could slow tumor growth and improve the effectiveness of existing immunotherapies in the future.