Collaborations with other laboratories are underway to assess the applicability of the MANAscore across various cancer types, leveraging a database of single-cell sequencing data to identify distinct responder T cell characteristics.
The MANAscore model not only pinpoints immune cells targeted by therapies but also highlights differences in patient responses to immunotherapy.
Understanding why not all patients respond to these therapies is crucial for developing improved treatments for nonresponders.
Immune checkpoint inhibitors, such as PD-1 inhibitors, reactivate T cells that fight cancer, but the variability in patient responses underscores the need for further investigation into the underlying reasons.
Researchers at Johns Hopkins Kimmel Cancer Center and the Bloomberg-Kimmel Institute for Cancer Immunotherapy have developed a groundbreaking computer model called 'MANAscore' to identify tumor-fighting immune cells in lung cancer patients undergoing treatment with immune checkpoint inhibitors.
Published on February 3, 2025, in Nature Communications, the study introduces the MANAscore, which distinguishes itself by utilizing only three genes to identify immune cells targeted by therapies, in contrast to other models that require over 200 genes.
This new model simplifies the identification process of tumor-active T cells, making it less time-consuming and cost-effective compared to previous methods.
The research indicates that patients who respond to therapy possess a higher proportion of stem-like memory T cells, which enhance their ability to generate effective anti-tumor responses.
These stem-like characteristics allow T cells to promote self-renewal and long-term persistence, contributing to sustained immune responses.
Zhen Zeng, Ph.D., the lead author, plans to explore how the proximity of T cells with the three-gene signature to other immune cells influences clinical outcomes.
Senior author Kellie Smith, Ph.D., emphasizes the importance of studying these identified T cells to improve biomarkers and targets for combination immunotherapy.
The study's authors have disclosed various conflicts of interest related to commercial partnerships and patents associated with their research.
