No abstract

No abstract

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

Background CD58 has been demonstrated to be abnormally expressed in multiple hematopoietic malignancies and solid tumors and plays an essential role in tumorigenesis and progression; however, its clinical significance and prognostic value in pancreatic ductal adenocarcinoma (PDAC) remain unknown. Methods Based on diverse online public databases and 81 PDAC samples of tissue microarray-based immunohistochemistry (IHC), we evaluated CD58 expression in PDAC patients and analyzed its association with clinicopathological characteristics, clinical outcomes, and infiltration of immune cells in PDAC. Furthermore, the correlation between CD58 and the cancer stem cell (CSC)-related, epithelial–mesenchymal transition (EMT)-related, and immune-related markers were detected. Besides, the functional enrichment analysis and related pathways were analyzed and visualized. Results CD58 expression was elevated in pancreatitis and PDAC tissues than normal pancreas or adjacent nontumor tissues. The positive cases of CD58 (e.g. more than 50% positive cells) in PDAC account for 95.06% (77/81). Upregulated CD58 in cancer tissues was associated with worse histological grade, larger tumor size, and poorer overall survival and disease-free survival in PDAC patients. Furthermore, Cox multivariate regression analysis revealed that CD58 was an independent prognostic factor in PDAC. CD58 expression was correlated with infiltrations of neutrophils, CD8+ T cells, and dendritic cells (DCs). In addition, correlation gene analysis indicated that CD58 expression was strongly correlated with immune-related, EMT-related, and CSC-related markers. Functional enrichment analysis and KEGG pathway manifested that CD58 might be involved in PDAC initiation and progression. Conclusions CD58 expression is upregulated in PDAC tissues and its high expression is notably related to poor survival of PDAC. Therefore, CD58 may serve as a novel and effective marker for predicting the prognosis of PDAC patients.

Background The clinical outcomes of patients who received distal pancreatectomy with splenectomy (DPS) and spleen-preserving distal pancreatectomy (SPDP) have been generally investigated. However, postoperative hematological changes after distal pancreatectomy with or without splenectomy are poorly understood. Methods Information from patients undergoing distal pancreatectomy (DP) between January 2014 and June 2019 at a single institution was reviewed. A linear mixed-effects model was used to compare dynamic hematological changes between different groups. Results A total of 302 patients who underwent DP were enrolled. In the long term, most postoperative hematological parameters remained significantly higher than preoperative levels in the DPS group, while postoperative lymphocyte, monocyte, basophil, and platelet levels returned to preoperative levels in the SPDP group. All postoperative hematological parameters except for red blood cell count and serum hemoglobulin level were significantly higher in the DPS group than in the SPDP group. There were no significant differences in hematological changes between the splenic vessel preservation (SVP) and Warshaw technique (WT) groups. Conclusions Postoperative hematological changes were significantly different between the DPS and SPDP groups. Compared to DPS, SPDP reduced abnormal hematological changes caused by splenectomy. SVP and WT were comparable in terms of postoperative hematological changes.

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

Background: The clinical outcomes of distal pancreatectomy with splenectomy (DPS) and spleen-preserving distal pancreatectomy (SPDP) patients have been generally investigated. However, postoperative hematological changes after distal pancreatectomy with or without splenectomy are poorly understood. Methods: Information from patients undergoing distal pancreatectomy (DP) between January 2014 and June 2019 at a single institution was reviewed. A linear mixed-effect model was used to compare dynamic hematological changes between different groups. Results: In total, 302 patients who underwent DP were enrolled. In the long term, most postoperative hematological parameters remained significantly higher than preoperative levels in the DPS group, while postoperative lymphocyte, monocyte, basophil, and platelet levels returned to preoperative levels in the SPDP group. All postoperative hematological parameters except for red blood cell count and serum hemoglobulin level were significantly higher in the DPS group than in the SPDP group. There were no significant differences in hematological changes between the splenic vessel preservation (SVP) and Warshaw technique (WT) groups. Conclusions: Postoperative hematological changes were significantly different between the DPS and SPDP groups. Compared to DPS, SPDP reduced abnormal hematological changes caused by splenectomy. SVP and WT were comparable in terms of postoperative hematological changes.

Background: The clinical outcomes of patients who received distal pancreatectomy with splenectomy (DPS) and spleen-preserving distal pancreatectomy (SPDP) have been generally investigated. However, postoperative hematological changes after distal pancreatectomy with or without splenectomy are poorly understood.Methods: Information from patients undergoing distal pancreatectomy (DP) between January 2014 and June 2019 at a single institution was reviewed. A linear mixed-effects model was used to compare dynamic hematological changes between different groups.Results: A total of 302 patients who underwent DP were enrolled. In the long term, most postoperative hematological parameters remained significantly higher than preoperative levels in the DPS group, while postoperative lymphocyte, monocyte, basophil, and platelet levels returned to preoperative levels in the SPDP group. All postoperative hematological parameters except for red blood cell count and serum hemoglobulin level were significantly higher in the DPS group than in the SPDP group. There were no significant differences in hematological changes between the splenic vessel preservation (SVP) and Warshaw technique (WT) groups.Conclusions: Postoperative hematological changes were significantly different between the DPS and SPDP groups. Compared to DPS, SPDP reduced abnormal hematological changes caused by splenectomy. SVP and WT were comparable in terms of postoperative hematological changes.