Immunotherapy for pancreatic cancer: A 2020 update

Schizas, Dimitrios; Charalampakis, Nikolaos; Kole, Christo; Economopoulou, Panagiota; Koustas, Evangelos; Gkotsis, Efthymios; Ziogas, Dimitrios C.; Psyrri, Amanda; Karamouzis, Michalis V.

doi:10.1016/j.ctrv.2020.102016

Cited by 295 publications

(231 citation statements)

References 98 publications

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“…In recent years, immunotherapy has gradually become one of the main therapies for various cancers due to beneficial enhancement of the immune function, decrease in the recurrence, and extension of survival (Xu F. et al, 2018;Gavrielatou et al, 2020;Schizas et al, 2020;Topalian et al, The results represent the mean ± SD, and **p < 0.01 was considered to be significant according to Student's t-test. (D) Expression levels of BAP31, Ki-67, and SERPINE2 in Hep3b subcutaneous tumors were monitored by IHC analysis.…”

Section: Discussionmentioning

confidence: 99%

BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma

Zhang

Jiang

Sun

et al. 2020

Front. Cell Dev. Biol.

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Hepatocellular carcinoma (HCC) patients are mostly diagnosed at an advanced stage, resulting in systemic therapy and poor prognosis. Therefore, the identification of a novel treatment target for HCC is important. B-cell receptor-associated protein 31 (BAP31) has been identified as a cancer/testis antigen; however, BAP31 function and mechanism of action in HCC remain unclear. In this study, BAP31 was demonstrated to be upregulated in HCC and correlated with the clinical stage. BAP31 overexpression promoted HCC cell proliferation and colony formation in vitro and tumor growth in vivo. RNA-sequence (RNA-seq) analysis demonstrated that serpin family E member 2 (SERPINE2) was downregulated in BAP31-knockdown HCC cells. Coimmunoprecipitation and immunofluorescence assays demonstrated that BAP31 directly binds to SERPINE2. The inhibition of SERPINE2 significantly decreased the BAP31-induced cell proliferation and colony formation of HCC cells and phosphorylation of Erk1/2 and p38. Moreover, multiplex immunohistochemistry staining of the HCC tissue microarray showed positive associations between the expression levels of BAP31, SERPINE2, its downstream gene LRP1, and a tumor proliferation marker, Ki-67. The administration of anti-BAP31 antibody significantly inhibited HCC cell xenograft tumor growth in vivo. Thus, these findings suggest that BAP31 promotes tumor cell proliferation by stabilizing SERPINE2 and can serve as a promising candidate therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma

Zhang

Jiang

Sun

et al. 2020

Front. Cell Dev. Biol.

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“…Traditional treatment methods (e.g., surgery, chemotherapy, radiotherapy, and other locoregional therapies) provide low survival rates. Currently, several clinical studies have focused on immunotherapeutic strategies in pancreatic cancer [ 20 ]. Therefore, a better understanding of the immune infiltration into pancreatic tumors and the identification of novel PDAC immune-related biomarkers may prove useful for immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Prognostic Biomarker and Its Correlation with Immune Infiltrates in Pancreatic Ductal Adenocarcinoma

Luan

Zhang

et al. 2020

Disease Markers

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Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor. The immune profile of PDAC and the immunologic milieu of its tumor microenvironment (TME) are unique; however, the mechanism of how the TME engineers the carcinogenesis of PDAC is not fully understood. This study is aimed at better understanding the relationship between the immune infiltration of the TME and gene expression and identifying potential prognostic and immunotherapeutic biomarkers for PDAC. Analysis of data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases identified differentially expressed genes (DEGs), including 159 upregulated and 53 downregulated genes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment were performed and showed that the DEGs were mainly enriched for the PI3K-Akt signaling pathway and extracellular matrix organization. We used the cytoHubba plugin of Cytoscape to screen out the most significant ten hub genes by four different models (Degree, MCC, DMNC, and MNC). The expression and clinical relevance of these ten hub genes were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. High expression of nine of the hub genes was positively correlated with poor prognosis. Finally, the relationship between these hub genes and tumor immunity was analyzed using the Tumor Immune Estimation Resource. We found that the expression of SPARC, COL6A3, and FBN1 correlated positively with infiltration levels of six immune cells in the tumors. In addition, these three genes had a strong coexpression relationship with the immune checkpoints. In conclusion, our results suggest that nine upregulated biomarkers are related to poor prognosis in PDAC and may serve as potential prognostic biomarkers for PDAC therapy. Furthermore, SPARC, COL6A3, and FBN1 play an important role in tumor-related immune infiltration and may be ideal targets for immune therapy against PDAC.

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“…Immunotherapy was stated to be the biggest breakthrough in cancer research in 2013 [ 81 ] and is also actively used in research for PDAC [ 82 ], but to date, its efficacy in PDAC is still limited [ 83 ]. More efforts are needed in this direction to overcome the immunosuppressive and therapy-resistant TME of PDAC [ 84 , 85 ] and to identify specific target molecules on cancer cells, without targeting normal cells [ 86 ].…”

Section: Pancreatic Ductal Adenocarcinoma (Pdac)mentioning

confidence: 99%

Cold Atmospheric Plasma Treatment for Pancreatic Cancer–The Importance of Pancreatic Stellate Cells

Verloy

Privat-Maldonado

Smits

et al. 2020

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with low five-year survival rates of 8% by conventional treatment methods, e.g., chemotherapy, radiotherapy, and surgery. PDAC shows high resistance towards chemo- and radiotherapy and only 15–20% of all patients can have surgery. This disease is predicted to become the third global leading cause of cancer death due to its significant rise in incidence. Therefore, the development of an alternative or combinational method is necessary to improve current approaches. Cold atmospheric plasma (CAP) treatments could offer multiple advantages to this emerging situation. The plasma-derived reactive species can induce oxidative damage and a cascade of intracellular signaling pathways, which could lead to cell death. Previous reports have shown that CAP treatment also influences cells in the tumor microenvironment, such as the pancreatic stellate cells (PSCs). These PSCs, when activated, play a crucial role in the propagation, growth and survival of PDAC tumors. However, the effect of CAP on PSCs is not yet fully understood. This review focuses on the application of CAP for PDAC treatment and the importance of PSCs in the response to treatment.

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Immunotherapy for pancreatic cancer: A 2020 update

Cited by 295 publications

References 98 publications

BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma

BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma

Identification of Key Prognostic Biomarker and Its Correlation with Immune Infiltrates in Pancreatic Ductal Adenocarcinoma

Cold Atmospheric Plasma Treatment for Pancreatic Cancer–The Importance of Pancreatic Stellate Cells

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