TAIPEI (TVBS News) — Imagine the body's immune system as a city's security network: lymph nodes serve as police stations, while specialized immune outposts near tumors function like neighborhood patrol teams coordinating attacks on cancer cells.
Taiwanese scientists have discovered that lung cancer jams these communications, hijacking pain-sensing nerves to broadcast false signals that prevent patrol teams from ever forming.
This neuro-immune mechanism, described Wednesday (July 8) in the journal Cell, offers a potential explanation for why immunotherapy — the revolutionary treatment that has transformed outcomes for some patients — fails for many lung cancer patients.
Why immunotherapy doesn't always work
Lung cancer remains the leading cause of cancer death worldwide, with lung adenocarcinoma being the most common subtype, accounting for approximately 70 percent of cases in Taiwan, according to National Taiwan University Hospital (臺大醫院).
Yet doctors have long observed that many patients show limited response to immunotherapy. The underlying reason has remained elusive — until now.
The research, led by Dr. Leanne Li (李力恩) of The Francis Crick Institute and conducted with National Taiwan University Hospital and Harvard Medical School, found that lung adenocarcinoma tumors attract large numbers of nociceptive neurons — specialized nerve cells sensing pain and harmful stimuli.
Once activated, these nerves release signaling molecules that suppress the formation of tertiary lymphoid structures — the immune system's "neighborhood patrol teams" that would otherwise gather near tumors to coordinate attacks on cancer cells.
A new approach: 'Cutting off the electricity'
Using mouse models, the research team demonstrated that blocking these nerve signals allowed the immune system's patrol structures to form again, significantly enhancing the body's ability to attack cancer cells.
Chen Jin-shing (陳晉興), chair of surgery at National Taiwan University Hospital, framed the findings as a dual strategy for fighting cancer during a press conference that day.
"Future cancer treatment should focus not only on 'cutting off the water supply' by targeting blood vessels that nourish tumors, but also on 'cutting off the electricity supply' by blocking nerve signals that promote cancer growth," Chen said in Taipei.
Certain medications already approved for treating migraines work by blocking the same nerve signals implicated in the study. In animal experiments, combining these drugs with immunotherapy strengthened anti-tumor immune responses and also prolonged survival.
Dr. Li said the next step will be clinical trials to evaluate whether this approach could become a new treatment option for advanced lung cancer.
Broader implications
The findings may extend beyond lung cancer. Research has shown nerve signaling plays a role in other cancers, including melanoma and pancreatic cancer.
The study also offers a new perspective on smoking. Beyond carcinogens causing genetic mutations, the research found that cigarette smoke directly activates pain-sensing nerves that weaken immune defenses, adding another layer to tobacco's cancer-causing effects.
Clinical trials in humans have not yet begun. ◼
