Frontiers in Immunology (Jun 2022)
Computational Recognition of a Regulatory T-cell-specific Signature With Potential Implications in Prognosis, Immunotherapy, and Therapeutic Resistance of Prostate Cancer
- Mingyi Ju,
- Mingyi Ju,
- Jingyi Fan,
- Jingyi Fan,
- Yuanjiang Zou,
- Yuanjiang Zou,
- Mingjie Yu,
- Mingjie Yu,
- Longyang Jiang,
- Longyang Jiang,
- Qian Wei,
- Qian Wei,
- Jia Bi,
- Jia Bi,
- Baohui Hu,
- Baohui Hu,
- Qiutong Guan,
- Qiutong Guan,
- Xinyue Song,
- Xinyue Song,
- Mingyan Dong,
- Mingyan Dong,
- Lin Wang,
- Lin Wang,
- Lifeng Yu,
- Lifeng Yu,
- Yan Wang,
- Yan Wang,
- Hui Kang,
- Wei Xin,
- Wei Xin,
- Lin Zhao,
- Lin Zhao
Affiliations
- Mingyi Ju
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Mingyi Ju
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Jingyi Fan
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Jingyi Fan
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Yuanjiang Zou
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Yuanjiang Zou
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Mingjie Yu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Mingjie Yu
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Longyang Jiang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Longyang Jiang
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Qian Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Qian Wei
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Jia Bi
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Jia Bi
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Baohui Hu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Baohui Hu
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Qiutong Guan
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Qiutong Guan
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Xinyue Song
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Xinyue Song
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Mingyan Dong
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Mingyan Dong
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Lin Wang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Lin Wang
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Lifeng Yu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Lifeng Yu
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Yan Wang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Yan Wang
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Hui Kang
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
- Wei Xin
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Wei Xin
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- Lin Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
- Lin Zhao
- Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
- DOI
- https://doi.org/10.3389/fimmu.2022.807840
- Journal volume & issue
-
Vol. 13
Abstract
Prostate cancer, recognized as a “cold” tumor, has an immunosuppressive microenvironment in which regulatory T cells (Tregs) usually play a major role. Therefore, identifying a prognostic signature of Tregs has promising benefits of improving survival of prostate cancer patients. However, the traditional methods of Treg quantification usually suffer from bias and variability. Transcriptional characteristics have recently been found to have a predictive power for the infiltration of Tregs. Thus, a novel machine learning-based computational framework has been presented using Tregs and 19 other immune cell types using 42 purified immune cell datasets from GEO to identify Treg-specific mRNAs, and a prognostic signature of Tregs (named “TILTregSig”) consisting of five mRNAs (SOCS2, EGR1, RRM2, TPP1, and C11orf54) was developed and validated to monitor the prognosis of prostate cancer using the TCGA and ICGC datasets. The TILTregSig showed a stronger predictive power for tumor immunity compared with tumor mutation burden and glycolytic activity, which have been reported as immune predictors. Further analyses indicate that the TILTregSig might influence tumor immunity mainly by mediating tumor-infiltrating Tregs and could be a powerful predictor for Tregs in prostate cancer. Moreover, the TILTregSig showed a promising potential for predicting cancer immunotherapy (CIT) response in five CIT response datasets and therapeutic resistance in the GSCALite dataset in multiple cancers. Our TILTregSig derived from PBMCs makes it possible to achieve a straightforward, noninvasive, and inexpensive detection assay for prostate cancer compared with the current histopathological examination that requires invasive tissue puncture, which lays the foundation for the future development of a panel of different molecules in peripheral blood comprising a biomarker of prostate cancer.
Keywords
- prostate cancer
- regulatory T cells (Tregs)
- cancer immunotherapy (CI)
- therapeutic resistance
- prognostic signature