PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification

BackgroundImmunogenic cell death (ICD) is a result of immune cell infiltration (ICI)-mediated cell death, which is also a novel acknowledgment to regulate cellular stressor-mediated cell death, including drug therapy and radiotherapy.MethodsIn this study, TCGA and GEO data cohorts were put into arti...

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Main Authors: Pengping Li, Wei Wang, Shaowen Wang, Guodong Cao, Tonghe Pan, Yuqing Huang, Hong Wan, Weijun Zhang, Yate Huang, Haigang Jin, Zhenyu Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1145481/full
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author Pengping Li
Wei Wang
Shaowen Wang
Guodong Cao
Tonghe Pan
Yuqing Huang
Hong Wan
Hong Wan
Weijun Zhang
Yate Huang
Haigang Jin
Zhenyu Wang
author_facet Pengping Li
Wei Wang
Shaowen Wang
Guodong Cao
Tonghe Pan
Yuqing Huang
Hong Wan
Hong Wan
Weijun Zhang
Yate Huang
Haigang Jin
Zhenyu Wang
author_sort Pengping Li
collection DOAJ
description BackgroundImmunogenic cell death (ICD) is a result of immune cell infiltration (ICI)-mediated cell death, which is also a novel acknowledgment to regulate cellular stressor-mediated cell death, including drug therapy and radiotherapy.MethodsIn this study, TCGA and GEO data cohorts were put into artificial intelligence (AI) to identify ICD subtypes, and in vitro experiments were performed.ResultsGene expression, prognosis, tumor immunity, and drug sensitivity showed significance among ICD subgroups, Besides, a 14-gene-based AI model was able to represent the genome-based drug sensitivity prediction, which was further verified in clinical trials. Network analysis revealed that PTPRC was the pivotal gene in regulating drug sensitivity by regulating CD8+ T cell infiltration. Through in vitro experiments, intracellular down-regulation of PTPRC enhanced paclitaxel tolerance in triple breast cancer (TNBC) cell lines. Meanwhile, the expression level of PTPRC was positively correlated with CD8+ T cell infiltration. Furthermore, the down-regulation of PTPRC increased the level of TNBC-derived PD-L1 and IL2.DiscussionICD-based subtype clustering of pan-cancer was helpful to evaluate chemotherapy sensitivity and immune cell infiltration, and PTPRC was a potential target to against drug resistance of breast cancer.
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spelling doaj.art-db5c654f122f4f65b824358b1082ff682023-06-14T05:36:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11454811145481PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratificationPengping Li0Wei Wang1Shaowen Wang2Guodong Cao3Tonghe Pan4Yuqing Huang5Hong Wan6Hong Wan7Weijun Zhang8Yate Huang9Haigang Jin10Zhenyu Wang11Department of Thyroid & Breast Surgery, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, ChinaDepartment of Oncology, The Second Affiliated Hospital of Bengbu Medical College, Anhui, ChinaNeuromedicine Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, ChinaThe Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaThe Department of Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, ChinaDepartment of Thyroid & Breast Surgery, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, ChinaThe Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaAnhui Public Health Clinical Center, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Thyroid & Breast Surgery, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, ChinaSchool of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Thyroid & Breast Surgery, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, ChinaDepartment of Thyroid & Breast Surgery, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, ChinaBackgroundImmunogenic cell death (ICD) is a result of immune cell infiltration (ICI)-mediated cell death, which is also a novel acknowledgment to regulate cellular stressor-mediated cell death, including drug therapy and radiotherapy.MethodsIn this study, TCGA and GEO data cohorts were put into artificial intelligence (AI) to identify ICD subtypes, and in vitro experiments were performed.ResultsGene expression, prognosis, tumor immunity, and drug sensitivity showed significance among ICD subgroups, Besides, a 14-gene-based AI model was able to represent the genome-based drug sensitivity prediction, which was further verified in clinical trials. Network analysis revealed that PTPRC was the pivotal gene in regulating drug sensitivity by regulating CD8+ T cell infiltration. Through in vitro experiments, intracellular down-regulation of PTPRC enhanced paclitaxel tolerance in triple breast cancer (TNBC) cell lines. Meanwhile, the expression level of PTPRC was positively correlated with CD8+ T cell infiltration. Furthermore, the down-regulation of PTPRC increased the level of TNBC-derived PD-L1 and IL2.DiscussionICD-based subtype clustering of pan-cancer was helpful to evaluate chemotherapy sensitivity and immune cell infiltration, and PTPRC was a potential target to against drug resistance of breast cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1145481/fullimmunogenic cell death (ICD)drug sensitivitybreast cancerPTPRCCD8+ T cell
spellingShingle Pengping Li
Wei Wang
Shaowen Wang
Guodong Cao
Tonghe Pan
Yuqing Huang
Hong Wan
Hong Wan
Weijun Zhang
Yate Huang
Haigang Jin
Zhenyu Wang
PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification
Frontiers in Immunology
immunogenic cell death (ICD)
drug sensitivity
breast cancer
PTPRC
CD8+ T cell
title PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification
title_full PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification
title_fullStr PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification
title_full_unstemmed PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification
title_short PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification
title_sort ptprc promoted cd8 t cell mediated tumor immunity and drug sensitivity in breast cancer based on pan cancer analysis and artificial intelligence modeling of immunogenic cell death based drug sensitivity stratification
topic immunogenic cell death (ICD)
drug sensitivity
breast cancer
PTPRC
CD8+ T cell
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1145481/full
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