Professor Kate Sutherland has spent years looking for a weak spot in one of the deadliest cancers there is. "For decades, we've known that small cell lung cancer is exceptionally good at hiding from the immune system," says Sutherland, a laboratory head at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne. Her team now believes it has found an immune cell that can see through that disguise.<\/p>\n
The cells are gamma delta T cells, a type of immune cell that has had little attention in research on this disease. The findings were published this month in the peer-reviewed journal Cancer Cell, with Dr Jin Ng as first author and Sutherland as senior author, working with the Doherty Institute, the Royal Melbourne Hospital and the Victorian Cancer Biobank.<\/p>\n
Small cell lung cancer accounts for roughly 10 to 15% of lung cancers. It grows fast, is linked to smoking and radon exposure, and fewer than 7% of patients are alive five years after diagnosis. Advanced cases are usually treated with chemotherapy plus immunotherapy, yet long-lasting responses are rare.<\/p>\n
Why does immunotherapy so often fail here? These tumours reduce the surface molecules that conventional T cells need to recognise them, so the cancer slips past unnoticed. Gamma delta T cells work differently: they pick up signs of stress in a diseased cell and do not depend on those molecules.<\/p>\n
To test the idea, the team grew miniature tumours in the lab from patient tissue given to the Victorian Cancer Biobank, models the researchers describe as among the most realistic yet made for this cancer. They then added gamma delta T cells taken from the same patients' blood. The immune cells recognised and killed the cancer cells efficiently. Using single-cell RNA sequencing and immune profiling, the researchers found gamma delta T cells in tissue from all twelve patients they analysed.<\/p>\n
The team also went back to two earlier immunotherapy trials, IMpower133 and CASPIAN. Patients whose tumours carried a stronger gamma delta T cell signature generally lived longer and gained more from immunotherapy given alongside chemotherapy. That is a statistical association, not proof that the cells themselves caused the longer survival.<\/p>\n
Two medicines already in use were tested as well. Zoledronate, approved for osteoporosis and cancer-related bone disease, raised gamma delta T cell counts and sharpened their ability to spot the tumour. Tarlatamab, approved for small cell lung cancer, drew the immune cells into closer contact with cancer cells. Together they markedly boosted the cancer-killing activity, though only in the lab; the combination has not been tried in patients. For people with lower levels of these cells, Ng said, "therapies such as zoledronate may offer a way to boost their cancer-fighting immune cells".<\/p>\n
Next, the group plans to work with the Doherty Institute on developing the results into a new kind of immunotherapy drug, and to look at adoptive transfer, in which a patient's gamma delta T cells are multiplied outside the body and infused back. The researchers say larger studies with more donated samples and animal models are needed to identify who might benefit and whether survival improves.<\/p>\n
The research was funded by Cancer Council Victoria, the National Health and Medical Research Council, the CASS Foundation and the International Association for the Study of Lung Cancer.<\/p>\n","protected":false},"excerpt":{"rendered":"
Professor Kate Sutherland has spent years looking for a weak spot in one of the deadliest cancers there is. "For decades, we've known that small cell lung cancer is exceptionally good at hiding from the immune system," says Sutherland, a laboratory head at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne. Her team now believes it has found an immune cell that can see through that disguise. The cells are gamma delta T cells, a type of immune cell that has had little attention in research on this disease. The findings were published this month in<\/p>\n","protected":false},"author":1,"featured_media":60903,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[13151],"tags":[],"class_list":["post-60902","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health"],"yoast_head":"\n