Immune subtyping for pancreatic cancer with implication in clinical outcomes and improving immunotherapy

Abstract Background Emerging evidence has shown that intra-tumor immune features are associated with response to checkpoint blockade (ICB) therapy. Accordingly, patient stratification is needed for identifying target patients and designing strategies improve the efficacy of ICB We aimed depict specific pancreatic cancer explore implication diversity in prognostic prediction individualized immunotherapy. Methods From transcriptional profiles 383 tumor samples TCGA, ICGC, GEO database, robust subtypes which had different immunotherapy, including therapy, were identified by consensus clustering five gene modules. DEGs analysis microarray used screen demonstrate potential targets improving Results Three cancer, namely cluster 1–3 (C1–C3), characterized distinct prognosis, generated. Of that, subtype C1 was an immune-cold type lack regulators, C2, immunosuppression-dominated phenotype TGF? signaling stromal reaction, showed worst C3 immune-hot type, massive cell infiltration abundance regulators. The disparity uncovered discrepant applicability anti-PD-1/PD-L1 therapy sensitivity other alternative immunotherapy each subtype. Patients more suitable while two clusters may need combined targeted on checkpoints or oncogenic pathways. A promising treatment, TGM2, screened out its role regulation PD-L1 investigated first time. Conclusion Collectively, contribute immunosuppressive mechanisms responsible Despite being considered as a poor immunogenic derived have implications tailored patients. TGM2 synergistic roles