Scientists Discover How Lung Cancer Weakens the Immune System

An international research team involving scientists from Taiwan has discovered a new mechanism used by lung cancer to weaken the body’s immune system. The study reveals that lung tumours can activate surrounding sensory nerves to inhibit the immune response, opening up opportunities for new approaches in cancer treatment.

The research, titled ‘Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer’, was published in the scientific journal Cell in mid-May. The study involved researchers from the Francis Crick Institute in the UK, National Taiwan University Hospital (NTUH), Harvard Medical School, and Columbia University.

Head of the Department of Surgery at NTUH, Chen Jin-shing, said the findings show a close relationship between the nervous system and the immune system in the development of lung cancer. According to him, the research opens up the possibility of treatment by blocking the nerve signals that help tumour growth.

In the study, scientists examined lung adenocarcinoma, a type that accounts for more than 70 per cent of lung cancer cases. The team found that as the tumour develops, nociceptive sensory nerves around the cancer become more active and release a molecule called calcitonin gene-related peptide (CGRP).

Normally, nociceptive nerves function to detect danger and help the body provide a protective response, such as triggering a cough when exposed to smoke. However, in lung cancer, this nerve activity is exploited by the tumour. The release of CGRP was found to inhibit the formation of tertiary lymphoid structures (TLS), which are clusters of immune cells that help the body attack cancer cells. The presence of TLS is associated with a stronger immune response and better treatment outcomes in lung cancer patients.

In experiments on mice, researchers found that blocking the CGRP pathway could restore TLS formation, increase immune activity against tumours, and slow cancer growth. The study also discovered that exposure to cigarette smoke can activate the same nerve pathway. This suggests that smoking not only increases cancer risk through genetic damage but may also affect the immune environment around the tumour. In mice exposed to cigarette smoke, drugs targeting the CGRP pathway made tumours more responsive to immunotherapy and improved survival rates.

Although promising, therapies based on this new mechanism have not yet entered human clinical trials. Researchers are continuing discussions to develop further studies. The findings provide a new perspective that lung cancer is not only influenced by genetic changes but also by complex interactions between the tumour, nerves, and the immune system.