Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

Zhuansun, Yongxun; Huang, Fengting; Feng, Min; Zhao, Xu; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

doi:10.2147/ott.s146383

Cited by 36 publications

(37 citation statements)

References 55 publications

(57 reference statements)

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“…The prevalence of therapy resistance to these treatments is a persistent problem. PDAC patients have not benefited from single agent or combination ICI therapy (194)(195)(196) despite increased expression of PD-L1 in tumors (197)(198)(199). Significant efforts are underway to improve immunotherapy efficacy, including studies investigating regulatory B cell inhibition (e.g., Bruton's Tyrosine Kinase (BTK) inhibitors), IDO inhibition, and vaccine therapy (200).…”

Section: Pancreatic Cancermentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

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Section: Pancreatic Cancermentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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“…Multiple human studies have indicated that high PD‐L1 expression in pancreatic cancer tumors is associated with worse outcomes suggesting that targeting the PD‐1/PD‐L1 interaction may have therapeutic benefit in these patients . An early preclinical study in a mouse tumor transplant model showed that PD‐1 or PD‐L1 blockade had an anti‐tumor effect which was enhanced when given together with gemcitabine .…”

Section: Limited Success Of Traditional Immunotherapymentioning

confidence: 99%

Immunotherapy for pancreatic cancer: Barriers and breakthroughs

Torphy¹,

Zhu²,

Schulick³

2018

Annals of Gastroent Surgery

131

116

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Immunotherapy is a rapidly growing field and represents a paradigm shift in the treatment of malignancies as it offers a new therapeutic approach beyond surgery, conventional chemotherapy, and radiation treatment. Targeting immune checkpoints, such as cytotoxic T‐lymphocyte‐associated antigen 4 and programmed death 1/programmed death ligand 1 has had immense clinical success resulting in sustained treatment response for a subset of patients with certain malignancies such as melanoma, non‐small‐cell lung cancer, urothelial carcinoma, squamous cell carcinoma of the head and neck, renal cell cancer, hepatocellular cancer, and metastatic colorectal cancer. Importantly, there has been limited success in the use of immunotherapy in the treatment of pancreatic cancer. Investigation into the complex tumor microenvironment of pancreatic cancer that is composed of immune cells, stromal cells, and extracellular matrix proteins has begun to shed light on important attributes of this microenvironment that act as barriers to the effective use of immunotherapy. In this review, we will discuss the progress that has been made in treating pancreatic cancer with immunotherapy, the barriers that have limited treatment success, and breakthroughs with combination treatments that hold promise for the future.

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“…It engages PD-1 to reverse activated T cell interaction with tumor cells and may also serve to induce apoptosis of T cells. Overexpression of PD-L1 is observed in melanoma ( Thierauf et al, 2015 ), pancreatic cancer ( Zhuan-Sun et al, 2017 ), oral cancer ( Goncalves et al, 2017 ), and colorectal cancer ( Droeser et al, 2013 ; Thierauf et al, 2015 ). It can be induced by thyroid hormone and other growth factors.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Anoectochilus formosanus Extract on Hyperglycemia-Related PD-L1 Expression and Cancer Proliferation

Chen

Wang

et al. 2018

Front. Pharmacol.

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Traditional herb medicine, golden thread (Anoectochilus formosanus Hayata) has been used to treat various diseases. Hyperglycemia induces generation of reactive oxygen species (ROS) and enhancement of oxidative stress which are risk factors for cancer progression and metastasis. In this study, we evaluated hypoglycemic effect of A. formosanus extracts (AFEs) in an inducible hyperglycemia animal model and its capacity of free-radical scavenging to establish hyperglycemia-related carcinogenesis. AFE reduced blood glucose in hyperglycemic mice while there was no change in control group. The incremental area under blood glucose response curve was decreased significantly in hyperglycemic mice treated with AFE in a dose-dependent manner. AFE and metformin at the same administrated dose of 50 mg/kg showed similar effect on intraperitoneal glucose tolerance test in hyperglycemic mice. Free-radical scavenger capacity of AFE was concentration dependent and 200 μg/ml of AFE was able to reduce more than 41% of the free radical. Treatment of cancer cells with AFE inhibited constitutive PD-L1 expression and its protein accumulation. It also induced expression of pro-apoptotic genes but inhibited proliferative and metastatic genes. In addition, it induced anti-proliferation in cancer cells. The results suggested that AFE not only reduced blood glucose concentration as metformin but also showed its potential use in cancer immune chemoprevention/therapy via hypoglycemic effect, ROS scavenging and PD-L1 suppression.

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Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

Cited by 36 publications

References 55 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Immunotherapy for pancreatic cancer: Barriers and breakthroughs

Inhibitory Effect of Anoectochilus formosanus Extract on Hyperglycemia-Related PD-L1 Expression and Cancer Proliferation

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