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

Immunogenic 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. In this study, TCGA and GEO data cohorts were put into artificial intellige...

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Bibliographic Details
Published in:Frontiers in immunology 2023-06, Vol.14, p.1145481-1145481
Main Authors: Li, Pengping, Wang, Wei, Wang, Shaowen, Cao, Guodong, Pan, Tonghe, Huang, Yuqing, Wan, Hong, Zhang, Weijun, Huang, Yate, Jin, Haigang, Wang, Zhenyu
Format: Article
Language:English
Subjects:
Artificial Intelligence
breast cancer
CD8+ T cell
CD8-Positive T-Lymphocytes
Drug Resistance
drug sensitivity
Humans
Immunogenic Cell Death
immunogenic cell death (ICD)
Immunology
Leukocyte Common Antigens
PTPRC
Triple Negative Breast Neoplasms
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Summary:Immunogenic 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. In this study, TCGA and GEO data cohorts were put into artificial intelligence (AI) to identify ICD subtypes, and in vitro experiments were performed. Gene 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. ICD-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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1145481