Lab-grown tumors reveal immune cells capable of killing small cell lung cancer

Researchers have identified a novel immune cell, known as gamma delta T cells, that can effectively recognize and kill small cell lung cancer (SCLC), the most aggressive form of lung cancer globally. Published in the journal Cancer Cell, the study conducted by the Walter and Eliza Hall Institute of Medical Research (WEHI) found that patients with higher levels of these specialized immune cells had better treatment outcomes.

This discovery could potentially open up new avenues for treating SCLC, a disease with a dismal five-year survival rate of less than 7%. Existing immunotherapy treatments have had limited success in combating SCLC, as the disease often evades detection by conventional immune cells. However, the WEHI study reveals that gamma delta T cells possess the ability to bypass this invisibility, suggesting they could serve as an alternative immune attack route for these hard-to-treat tumors.

To validate their findings, researchers generated lab-based SCLC tumors using patient samples from the Victorian Cancer Biobank, collaborating with the Royal Melbourne Hospital. When these mini-tumors were combined with gamma delta T cells derived from patients' own blood, the immune cells demonstrated remarkable efficacy in identifying and eliminating SCLC cells.

Moreover, the research team discovered that two existing drugs—tarlatamab, approved for SCLC treatment, and zoledronate, used for osteoporosis and cancer-related bone disease—could boost the cancer-fighting capabilities of these immune cells. Combining zoledronate with tarlatamab significantly enhanced the gamma delta T cells' ability to attack SCLC cells, indicating a potential new strategy to strengthen anticancer immunity in SCLC patients.

The study's senior author, Dr. Kate Sutherland, highlighted that these findings could help address one of the field's most pressing questions: how to improve the response rate of lung cancer patients to immunotherapy. Dr. Jin Ng, the study's first author, suggested that therapies aimed at expanding and reinfusing gamma delta T cells might offer a promising approach for patients with lower levels of these immune cells, potentially improving their responsiveness to treatments.

The researchers emphasized that their findings could pave the way for personalized treatment strategies in SCLC and other solid cancers that are often missed by conventional immune cells.