Dataset Information

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.

SUBMITTER: Luo Y

PROVIDER: S-EPMC9596778 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Luo Yang Y Zong Yunfeng Y Hua Hanju H Gong Meiting M Peng Qiao Q Li Chen C Neculai Dante D Zeng Xun X

Frontiers in immunology 20221012

<h4>Background</h4>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.<h4>Methods</h4>We developed a scoring system based on immun ...[more]

PMID: 36311750

Similar Datasets

Project description:BackgroundTumour-infiltrating lymphocytes (TILs), including T and B cells, have been demonstrated to be associated with tumour progression. However, the different subpopulations of TILs and their roles in breast cancer remain poorly understood. Large-scale analysis using multiomics data could uncover potential mechanisms and provide promising biomarkers for predicting immunotherapy response.MethodsSingle-cell transcriptome data for breast cancer samples were analysed to identify unique TIL subsets. Based on the expression profiles of marker genes in these subsets, a TIL-related prognostic model was developed by univariate and multivariate Cox analyses and LASSO regression for the TCGA training cohort containing 1089 breast cancer patients. Multiplex immunohistochemistry was used to confirm the presence of TIL subsets in breast cancer samples. The model was validated with a large-scale transcriptomic dataset for 3619 breast cancer patients, including the METABRIC cohort, six chemotherapy transcriptomic cohorts, and two immunotherapy transcriptomic cohorts.ResultsWe identified two TIL subsets with high expression of CD103 and LAG3 (CD103+LAG3+), including a CD8+ T-cell subset and a B-cell subset. Based on the expression profiles of marker genes in these two subpopulations, we further developed a CD103+LAG3+ TIL-related prognostic model (CLTRP) based on CXCL13 and BIRC3 genes for predicting the prognosis of breast cancer patients. CLTRP-low patients had a better prognosis than CLTRP-high patients. The comprehensive results showed that a low CLTRP score was associated with a high TP53 mutation rate, high infiltration of CD8 T cells, helper T cells, and CD4 T cells, high sensitivity to chemotherapeutic drugs, and a good response to immunotherapy. In contrast, a high CLTRP score was correlated with a low TP53 mutation rate, high infiltration of M0 and M2 macrophages, low sensitivity to chemotherapeutic drugs, and a poor response to immunotherapy.ConclusionsOur present study showed that the CLTRP score is a promising biomarker for distinguishing prognosis, drug sensitivity, molecular and immune characteristics, and immunotherapy outcomes in breast cancer patients. The CLTRP could serve as a valuable tool for clinical decision making regarding immunotherapy.

Project description:BackgroundColorectal cancer (CRC) ranks among the most prevalent malignancies affecting the gastrointestinal tract. The infiltration of CD8+ T cells significantly influences the prognosis and progression of tumor patients.MethodsThis study establishes a CRC immune risk model based on CD8+ T cell-related genes. CD8+ T cell-related genes were identified through Weighted Gene Co-expression Network Analysis (WGCNA), and the enriched gene sets were annotated via Gene Ontology (GO) and Reactome pathway analysis. Employing machine learning methods, including the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Random Forest (RF), we identified nine genes associated with CD8+ T-cell infiltration. The infiltration levels of immune cells in CRC tissues were assessed using the ssGSEA algorithm.ResultsThese genes provide a foundation for constructing a prognostic model. The TCGA-CRC sample model's prediction scores were categorized, and the prediction models were validated through Cox regression analysis and Kaplan-Meier curve analysis. Notably, although CRC tissues with higher risk scores exhibited elevated levels of CD8+ T-cell infiltration, they also demonstrated heightened expression of immune checkpoint genes. Furthermore, comparison of microsatellite instability (MSI) and gene mutations across the immune subgroups revealed notable gene variations, particularly with APC, TP53, and TNNT1 showing higher mutation frequencies. Finally, the predictive model's efficacy was corroborated through the use of Tumor Immune Dysfunction and Exclusion (TIDE), Immune Profiling Score (IPS), and immune escape-related molecular markers. The predictive model was validated through an external cohort of CRC and the Bladder Cancer Immunotherapy Cohort. CLRN3 expression levels in tumor and adjacent normal tissues were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Subsequent in vitro and in vivo experiments demonstrated that CLRN3 knockdown significantly attenuated the malignant biological behavior of CRC cells, while overexpression had the opposite effect.ConclusionsThis study presents a novel prognostic model for CRC, providing a framework for enhancing the survival rates of CRC patients by targeting CD8+ T-cell infiltration.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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