Study reveals role of gamma-delta T cells in cancer immunology

A new study published in Cell Reports Medicine reveals essential insights into the role of gamma-delta T cells in 33 cancer types, highlighting their potential as clinical biomarkers and therapeutic targets in cancer treatment. Led by a team of researchers at Moffitt Cancer Center, this comprehensive analysis represents a significant advance in understanding these unique immune cells and their implications for patient outcomes in cancer treatment.

Despite their minority status within the T cell community, gamma-delta T cells are increasingly recognized for their dual capacity to engage innate and adaptive immune responses. Moffitt researchers, in collaboration with scientists from Dartmouth College and Duke University, used a new computer algorithm to analyze the gamma-delta T cell receptor landscape in 11,000 tumors, providing an expanded database which tracks cancer progression and responses to various treatments, particularly immunotherapy. .

“It’s like finding a needle in a haystack,” said Xuefeng Wang, Ph.D., chair of Moffitt’s department of biostatistics and bioinformatics and the study’s primary contact. “After two years of effort examining approximately 700 billion tumor RNA sequencing reads, our algorithm distilled 3.2 million gamma-delta T cell reads, highly informative for the study of gamma T cell clones -delta. Our results suggest that the diversity and clonality of gamma-delta T cells may have a significant impact on patient survival and treatment efficacy.

The main findings of the study include:

• Database Creation: The research produced a comprehensive database of gamma-delta T cell receptor sequences across multiple cancers, providing a valuable resource for ongoing research into these immune components.
• Potential Biomarkers: The analysis identified several genes that could serve as prognostic biomarkers, varying significantly across different cancer types, including head and neck squamous cell carcinoma and colorectal adenocarcinoma.
• Immunotherapy Response: The study found that higher gamma-delta T cell receptor genetic enrichment scores correlate with better responses to immunotherapy, highlighting the need for personalized therapeutic approaches incorporating gamma-delta T cell signatures.
• Tumor microenvironment: Research indicates that gamma-delta T cells are often enriched in tumor microenvironments compared to normal tissues, suggesting that they may play a unique role in immune surveillance.
• Context-specific roles: The study emphasizes the complexity of gamma-delta T cell contributions, noting that their impact on disease progression varies depending on the molecular characteristics of the tumor and patient context.

As the study evolves, researchers will expand the database by incorporating additional T cell receptor repertoires and functional annotations, including single-cell RNA sequencing analyses. This ongoing work aims to deepen our understanding of the functional roles of gamma-delta T cells in cancer and their interactions within the tumor microenvironment.

“This research not only expands our knowledge of gamma-delta T cells, but also opens new avenues for therapeutic strategies,” Wang said. “By understanding the specific roles of these cells in different cancers, we can better tailor treatments to improve patient outcomes.”