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

Abstract

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.