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Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Pan-cancer analysis identifies CD300 molecules as potential immune regulators and promising therapeutic targets in
Zi-Jun Xu1,2,3, Ye Jin2,4, Xin-Long Zhang5
1Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Background:
CD300s are a group of proteins playing vital roles in immune responses. However, much is yet to be elucidated regarding the expression patterns and clinical significances of CD300s in cancers.
Methods:
In this study, we comprehensively investigated CD300s in a pan-cancer manner using multi-omic data from The Cancer Genome Atlas. We also studied the relationship between CD300s and the immune landscape of AML.
Results:
We found that CD300A-CD300LF were generally overexpressed in tumors (especially AML), whereas CD300LG was more often downregulated. In AML, transactivation of CD300A was not mediated by genetic alterations but by histone modification. Survival analyses revealed that high CD300A-CD300LF expression predicted poor outcome in AML patients; the prognostic value of CD300A was validated in seven independent datasets and a meta dataset including 1115 AML patients. Furthermore, we demonstrated that CD300A expression could add prognostic value in refining existing risk models in AML. Importantly, CD300A-CD300LF expression was closely associated with T-cell dysfunction score and could predict response to AML immunotherapy. Also, CD300A was found to be positively associated with HLA genes and critical immune checkpoints in AML, such as VISTA, CD86, CD200R1, Tim-3, and the LILRB family genes.
Conclusions:
Our study demonstrated CD300s as potential prognostic biomarker and an ideal immunotherapy target in AML, which warrants future functional and clinical studies.
Insights
CD300 proteins are key in immune responses. High CD300A and CD300LF expression in acute myeloid leukemia (AML) predicts poor outcomes and suggests potential as immunotherapy targets.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- CD300 proteins are crucial for immune responses.
- Their expression and clinical significance in cancers, particularly acute myeloid leukemia (AML), remain largely unknown.
Purpose of the Study:
- To investigate the expression patterns and clinical significance of CD300 family members in a pan-cancer context.
- To explore the relationship between CD300s and the immune landscape in AML.
- To evaluate CD300s as prognostic biomarkers and immunotherapy targets in AML.
Main Methods:
- Utilized multi-omic data from The Cancer Genome Atlas (TCGA) for pan-cancer analysis.
- Investigated CD300 expression, genetic alterations, and epigenetic modifications (histone modification) in AML.
- Performed survival analyses and validated prognostic value in independent AML datasets.
- Assessed associations with immune landscape features, T-cell dysfunction, and immunotherapy response in AML.
Main Results:
- CD300A-CD300LF were overexpressed in tumors, especially AML, while CD300LG was downregulated.
- CD300A upregulation in AML was linked to histone modification, not genetic alterations.
- High CD300A-CD300LF expression correlated with poor prognosis in AML patients.
- CD300A expression improved existing AML risk models and predicted immunotherapy response.
- CD300A-CD300LF expression associated with T-cell dysfunction, HLA genes, and immune checkpoints in AML.
Conclusions:
- CD300 proteins, particularly CD300A and CD300LF, show potential as prognostic biomarkers in AML.
- CD300s represent promising targets for immunotherapy in AML.
- Further functional and clinical studies are warranted to validate these findings.
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