A new study published in Celpers reveals critical insights into the role of gamma-delta T cells in 33 types of cancer, shedding light on 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 the understanding of these unique immune cells and their implications for patient cancer therapy outcomes.

Despite their minority status within the T cell community, gamma-delta T cells are increasingly recognized for their dual ability to engage in both innate and adaptive immune responses. Moffitt researchers, in collaboration with scientists from Dartmouth College and Duke University, used a new computational algorithm to analyze the gamma-delta T cell receptor landscape of 11,000 tumors, creating a comprehensive database that tracks cancer progression and responses to various treatments, especially immunotherapy, follows. .

“It’s like finding a needle in a haystack,” says Xuefeng Wang, Ph.D., chair of Moffitt’s Department of Biostatistics and Bioinformatics and lead liaison on the study. “After two years of effort to screen 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-delta T cell clones. Our findings suggest that the diversity and clonality of gamma-delta T cells can significantly influence patient survival and treatment efficacy.”

Key findings of the study include:

  • Database creation: The study provided a comprehensive database of gamma-delta T cell receptor sequences for multiple cancer types, providing a valuable resource for ongoing research into these immune components.
  • Potential biomarkers: The analysis identified several genes that may serve as prognostic biomarkers, which vary significantly between different types of cancer, including squamous cell carcinoma of the head and neck and colorectal adenocarcinoma.
  • Immunotherapy Response: The study found that higher gamma-delta T-cell receptor gene enrichment scores correlate with better responses to immunotherapy, highlighting the need for personalized treatment approaches that incorporate gamma-delta T-cell signatures.
  • Tumor microenvironment: The study shows that gamma-delta T cells are often enriched in the tumor microenvironment compared to normal tissues, suggesting that they may play a unique role in immune surveillance.
  • Context-specific roles: The study highlights the complexity of the contributions of gamma-delta T cells, noting that their impact on disease progression varies based on the molecular characteristics of the tumor and the patient’s context.

As research progresses, researchers will expand the database to include 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,” said Wang. “By understanding the specific roles of these cells in different cancers, we can better tailor treatments to improve patient outcomes.”

The Immuno-Oncology Program and shared biostatistics and bioinformatics resources at Moffitt provided critical support and represent leading research expertise in computational immunology and personalized immunotherapy.

This study was supported by the National Institutes of Health (R01DE030493 and P20GM130454) and the National Cancer Institute (P30-CA076292).