Dilemma and Challenge of Immunotherapy for Pancreatic Cancer

Wu, Jia; Cai, Jianting

doi:10.1007/s10620-020-06183-9

Cited by 51 publications

(41 citation statements)

References 94 publications

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“…Improving our understanding of how PAAD immune and stromal components interact and the tumor microenvironment can help improve our immunotherapy [51,52]. Future strategies using immunotherapy to treat pancreatic cancer include changing immune checkpoint inhibitors from monotherapy to combination therapy and combining immunotherapy with chemotherapy, radiation therapy, and targeted therapy [53]. Due to the obvious heterogeneity among individuals with PAAD, the uses of immunotherapy will be based on the results of genetic testing, so that a personalized treatment plan can be implemented to improve the efficacy of the treatment [54].…”

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confidence: 99%

Identification of Prognostic Immune-Related Genes in Pancreatic Adenocarcinoma and Establishment of a Prognostic Nomogram: A Bioinformatic Study

Deng

Jin

et al. 2020

BioMed Research International

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Background. The prognosis of pancreatic adenocarcinoma (PAAD) is extremely poor and has not been improved. Thus, an effective method to assess the prognosis of patients must be established to improve their survival rate. Method. This study investigated immune-related genes that could be used as potential therapeutic targets for PAAD. Level 3 gene expression data from the PAAD cohort and the relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. For validation, other PAAD datasets (DSE62452) were downloaded from the Gene Expression Omnibus (GEO) database. The PAAD datasets from TCGA and GEO were used to screen immune-related genes through the Molecular Signatures Database using gene set enrichment analysis. Then, the overlapping immune-related genes of the two datasets were identified. Coexpression networks of the immune-related genes were constructed. Results. A signature of three immune-related genes (CKLF, ERAP2, and EREG) was identified in patients with PAAD. The signature could be used to divide the patients with PAAD into high- and low-risk groups based on their median risk score. Multivariate Cox regression analysis was performed to determine the independent prognostic factors of PAAD. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. Last, a nomogram was established to assess the individualized prognosis prediction model based on the clinical characteristics and risk score of the TCGA PAAD dataset. The accuracy of the prognostic signature was further evaluated through functional evaluation and principal component analysis. Conclusions. The results indicated that the signature of three immune-related genes had excellent predictive value for PAAD. These findings might help improve personalized treatment and medical decisions.

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confidence: 99%

Identification of Prognostic Immune-Related Genes in Pancreatic Adenocarcinoma and Establishment of a Prognostic Nomogram: A Bioinformatic Study

Deng

Jin

et al. 2020

BioMed Research International

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“…Immunotherapies that have received FDA approval for use in other tumors to date have little to no efficacy against this cancer. The problem lies in its strikingly immunosuppressive and "immune privileged" tumor microenvironment, where few patients exhibit robust T-cell infiltration (32). Thus, pancreatic cancer has been classically described as a "cold" tumor because it is characterized by a relative paucity of intratumoral CD8 + T cells (33).…”

Section: Discussionmentioning

confidence: 99%

PARP Inhibitor Upregulates PD-L1 Expression and Provides a New Combination Therapy in Pancreatic Cancer

et al. 2021

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Despite recent improvements in treatment modalities, pancreatic cancer remains a highly lethal tumor with mortality rate increasing every year. Poly (ADP-ribose) polymerase (PARP) inhibitors are now used in pancreatic cancer as a breakthrough in targeted therapy. This study focused on whether PARP inhibitors (PARPis) can affect programmed death ligand-1 (PD-L1) expression in pancreatic cancer and whether immune checkpoint inhibitors of PD-L1/programmed death 1 (PD-1) can enhance the anti-tumor effects of PARPis. Here we found that PARPi, pamiparib, up-regulated PD-L1 expression on the surface of pancreatic cancer cells in vitro and in vivo. Mechanistically, pamiparib induced PD-L1 expression via JAK2/STAT3 pathway, at least partially, in pancreatic cancer. Importantly, pamiparib attenuated tumor growth; while co-administration of pamiparib with PD-L1 blockers significantly improved the therapeutic efficacy in vivo compared with monotherapy. Combination therapy resulted in an altered tumor immune microenvironment with a significant increase in windiness of CD8+ T cells, suggesting a potential role of CD8+ T cells in the combination therapy. Together, this study provides evidence for the clinical application of PARPis with anti-PD-L1/PD-1 drugs in the treatment of pancreatic cancer.

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“…However, health-related quality of life data during CRT supported the use of gemcitabine-based chemoradiation (35). Pancreatic cancer is a typical hypovolemic tumor in which conventional systemic chemotherapy has a low dose of drugs reaching the tumor tissue (36). The high expression of the multidrug resistance genes in pancreatic cancer cells makes pancreatic cancer less sensitive to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

et al. 2021

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Insertion of radioactive strips through the biliary stent has been reported to offer longer survival and patency than an uncovered conventional self-expanding metal stent in patients with unresectable malignant biliary obstruction. The aim of this study was to investigate the safety and effectiveness of intraluminal brachytherapy combined with 125 I seed implantation and transarterial infusion chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice. METHOD: From October 2012 to January 2018, 21 consecutive patients diagnosed with biliary obstruction caused by locally advanced, nonmetastatic pancreatic cancer with cytologically or histologically confirmed by biopsy were enrolled and receive treatment with intraluminal brachytherapy using 125 I seed strand and CT-guided percutaneous radioactive seed implantation therapy. The procedure-related and radiation complications were assessed. The outcomes were measured in terms of stent patency, patient survival, complications related to the procedure. RESULT: One of the 22 patients (4.5%, 1/22) with pancreatic head cancer failed to perform the above procedure because the guidewire was unable to pass through the obstruction segment. The remaining 21 patients (95.5%, 21/22) with pancreatic head cancer with obstructive jaundice were successfully placed with biliary stents and radioactive strips through drainage tubes. The median number of 125 I seeds loaded was 15, ranging from 12 to 17. After the chemotherapy with gemcitabine and cisplatin, no adverse reaction of Grade III~Ⅳ occurred in all cases. Median stent patency was 12.50 months (95% CI: 10.26, 14.74). By May 2019, all 21 patients had died, with overall survival of 5.2e23.3 months, with a median survival of 13.20 months (95% CI: 10.96, 15.44). CONCLUSION: Percutaneous 125 I seed implantation combined with insertion of radioactive strips through the biliary stent has the characteristics of less trauma, fewer complications, simple operation, and so on. These procedures bring remission of obstructive jaundice combined with the increased survival for the treatment of obstructive jaundice caused by unresectable pancreatic head cancer if follow-up chemotherapy is carried out. The long-term efficacy of this treatment combination needs to be confirmed by further multicenter, large sample size prospective randomized controlled studies.

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Dilemma and Challenge of Immunotherapy for Pancreatic Cancer

Cited by 51 publications

References 94 publications

Identification of Prognostic Immune-Related Genes in Pancreatic Adenocarcinoma and Establishment of a Prognostic Nomogram: A Bioinformatic Study

Identification of Prognostic Immune-Related Genes in Pancreatic Adenocarcinoma and Establishment of a Prognostic Nomogram: A Bioinformatic Study

PARP Inhibitor Upregulates PD-L1 Expression and Provides a New Combination Therapy in Pancreatic Cancer

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

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