2021
DOI: 10.1158/1078-0432.ccr-18-0900
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Immunotherapy in Pancreatic Adenocarcinoma: Beyond “Copy/Paste”

Abstract: Immunotherapy has dramatically changed the cancer treatment landscape during the past decade, but very limited efficacy has been reported against pancreatic cancer. Several factors unique to pancreatic cancer may explain the resistance: the well-recognized suppressive elements in the tumor microenvironment, the functional and structural barrier imposed by the stroma components, T cell exhaustion, the choice of perhaps the wrong immune targets, and microbial factors including gut dysbiosis and the unexpected pr… Show more

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Cited by 32 publications
(29 citation statements)
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References 131 publications
(133 reference statements)
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“…However, to date, a limited fraction of individuals with pancreatic cancer appear to have actionable genetic alterations, including BRCA1 and BRCA2 mutations, neurotrophic receptor tyrosine kinase (NTRK) gene fusions, and microsatellite instability (MSI)-high [11,17,[21][22][23][24][25][26]. In addition, the single use of immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PDCD1), CD274 (also known as programmed cell death 1 ligand 1, PD-L1, or B7-H1), and cytotoxic T lymphocyte-associated protein 4 (CTLA4) has shown no effectiveness in metastatic pancreatic cancers [27]. Therefore, many preclinical and translational studies are ongoing to discover potential vulnerabilities and therapeutic opportunities to treat PDAC [28][29][30].…”
Section: Introductionmentioning
confidence: 99%
“…However, to date, a limited fraction of individuals with pancreatic cancer appear to have actionable genetic alterations, including BRCA1 and BRCA2 mutations, neurotrophic receptor tyrosine kinase (NTRK) gene fusions, and microsatellite instability (MSI)-high [11,17,[21][22][23][24][25][26]. In addition, the single use of immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PDCD1), CD274 (also known as programmed cell death 1 ligand 1, PD-L1, or B7-H1), and cytotoxic T lymphocyte-associated protein 4 (CTLA4) has shown no effectiveness in metastatic pancreatic cancers [27]. Therefore, many preclinical and translational studies are ongoing to discover potential vulnerabilities and therapeutic opportunities to treat PDAC [28][29][30].…”
Section: Introductionmentioning
confidence: 99%
“…Meanwhile, immunotherapy treatment efficacy is limited in pancreatic cancer because of the functional and structural barrier imposed by the stroma components. 40 So bodies of cell death induced by pyroptosis may contribute to the structural barrier in the tumor microenvironment.…”
Section: Discussionmentioning
confidence: 99%
“…Drug development in PDAC is challenging, as modest results of immunotherapy in this pathology points out. Although several reasons for this lack of results have been proposed (49), the inclusion of unselected patients in clinical trials, regarding its molecular features, may be a hidden factor, point out the need of taking molecular heterogeneity of PDAC into account in future developments. Our results suggest some therapeutic strategies to follow up in each proteomics subtype.…”
Section: Discussionmentioning
confidence: 99%