Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer

CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar t...

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Main Authors: Mabel Vidal, Marco Fraga, Faryd Llerena, Agustín Vera, Mauricio Hernández, Elard Koch, Felipe Reyes-López, Eva Vallejos-Vidal, Guillermo Cabrera-Vives, Estefanía Nova-Lamperti
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/19/11065
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author Mabel Vidal
Marco Fraga
Faryd Llerena
Agustín Vera
Mauricio Hernández
Elard Koch
Felipe Reyes-López
Eva Vallejos-Vidal
Guillermo Cabrera-Vives
Estefanía Nova-Lamperti
author_facet Mabel Vidal
Marco Fraga
Faryd Llerena
Agustín Vera
Mauricio Hernández
Elard Koch
Felipe Reyes-López
Eva Vallejos-Vidal
Guillermo Cabrera-Vives
Estefanía Nova-Lamperti
author_sort Mabel Vidal
collection DOAJ
description CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.
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spelling doaj.art-4d240eb2e48043d2bb88e6cbeb0f9d212023-11-23T20:26:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191106510.3390/ijms231911065Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of CancerMabel Vidal0Marco Fraga1Faryd Llerena2Agustín Vera3Mauricio Hernández4Elard Koch5Felipe Reyes-López6Eva Vallejos-Vidal7Guillermo Cabrera-Vives8Estefanía Nova-Lamperti9Department of Computer Science, Universidad de Concepción, Concepción 4070409, ChileMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción 4070386, ChileMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción 4070386, ChileMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción 4070386, ChileDivision of Biotechnology, MELISA Institute, Concepción 4133515, ChileDivision of Biotechnology, MELISA Institute, Concepción 4133515, ChileCentro de Biotecnologia Acuicola, Departamento de Biologia, Facultad de Quimica y Biologia, Universidad de Santiago de Chile, Santiago 9170022, ChileNúcleo de Investigación Aplicada en Ciencias Veterinarias y Agronómicas, Facultad de Medicina Veterinaria y Agronomía, Universidad de Las Américas, Santiago 7500975, ChileDepartment of Computer Science, Universidad de Concepción, Concepción 4070409, ChileMolecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción 4070386, ChileCD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.https://www.mdpi.com/1422-0067/23/19/11065single-cell RNA-seqcancerT-cellimmunopathologymetabolic pathwaysviral pathways
spellingShingle Mabel Vidal
Marco Fraga
Faryd Llerena
Agustín Vera
Mauricio Hernández
Elard Koch
Felipe Reyes-López
Eva Vallejos-Vidal
Guillermo Cabrera-Vives
Estefanía Nova-Lamperti
Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer
International Journal of Molecular Sciences
single-cell RNA-seq
cancer
T-cell
immunopathology
metabolic pathways
viral pathways
title Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer
title_full Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer
title_fullStr Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer
title_full_unstemmed Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer
title_short Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer
title_sort analysis of tumor infiltrating t cell transcriptomes reveal a unique genetic signature across different types of cancer
topic single-cell RNA-seq
cancer
T-cell
immunopathology
metabolic pathways
viral pathways
url https://www.mdpi.com/1422-0067/23/19/11065
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