Immune-infiltrating signature-based classification reveals CD103+CD39+ T cells associate with colorectal cancer prognosis and response to immunotherapy

Abstract

Background: Current stratification systems for tumor prognostic prediction and immunotherapeutic efficacy evaluation are less satisfying in colorectal cancer (CRC). As infiltrating immune cells in tumor microenvironment (TME) played a key role in tumor progression and responses to immune checkpoint blockade (ICB) therapy, we want to construct an immune-related scoring system with detailed immune profiles to stratify CRC patients.

Methods: We developed a scoring system based on immune-related signatures and validated its ability to predict prognosis and immunotherapeutic outcomes in CRC. CD45⁺ cells from CRC patients were sorted to investigate detailed immune profiles of the stratification system using mass cytometry. A single-cell RNA sequencing dataset was used to analyze transcriptomic profiles.

Results: We constructed an immune-related signature score (IRScore) based on 54 recurrence-free survival (RFS)-related immune signatures to stratify CRC patients. We revealed that IRScore was positively correlated with RFS and favorable outcomes in ICB treatment. Moreover, we depicted a detailed immune profile in TME using mass cytometry and identified that CD103⁺CD39⁺ T cells, characterized by an exhaustive, cytotoxic and proliferative phenotype, were enriched in CRC patients with high IRScore. As a beneficial immune signature, CD103⁺CD39⁺ T cells could predict prognosis and responses to ICB therapy in CRC.

Conclusions: All the analyses above revealed that IRScore could be a valuable tool for predicting prognosis and facilitating the development of new therapeutic strategies in CRC, and CD103⁺CD39⁺ T cells were one of defined immune signatures in IRScore, which might be a key factor for antitumor immunity.

Keywords: colorectal cancer; high-dimensional single-cell analysis; immune cell diversity; immunotherapy; prognosis.