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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Frontiers Media S.A.
2023-06-01
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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. |
first_indexed | 2024-03-13T05:38:00Z |
format | Article |
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institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-03-13T05:38:00Z |
publishDate | 2023-06-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Immunology |
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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