Effectiveness and safety of PD-1/PD-L1 or CTLA4 inhibitors combined with chemotherapy as a first-line treatment for lung cancer: A meta-analysis

Shen, Kaikai; Cui, Jinggang; Wei, Yuqing; Chen, Xiaojun; Li, Guohua; Xiao-lai, Gao; Li, Wei; Lü, Huiling; Zhan, Ping; Lv, Tangfeng; Lin, Dong

doi:10.21037/jtd.2018.11.72

Cited by 36 publications

(21 citation statements)

References 52 publications

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“…A549 cells or A549/DDP cells (1 × 10 5 ) were infected with 1 × 10 6 recombinant lentivirus-transducing units in the presence of 6 μg/mL polybrene (Sigma, Shanghai, China Tumor growth was examined every three days. After 5~7 days, the tumor volume grew to ≈100 mm 3 , and the mice were intraperitoneally injected with a suspension of PBS containing DDP (2.5 mg/kg) twice per week. All mice were sacrificed after 4 weeks.…”

Section: Lentivirus Infectionmentioning

confidence: 99%

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Elevated Glutathione Peroxidase 2 Expression Promotes Cisplatin Resistance in Lung Adenocarcinoma

Jiao

et al. 2020

Oxidative Medicine and Cellular Longevity

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The aim of this study was to explore the roles of GPX2, a member of the glutathione peroxidase family (GPXs, GSH-Px), in cisplatin (DDP) resistance in lung adenocarcinoma (LUAD). GPX2 was found to be the most significantly upregulated gene in a DDP-resistant A549/DDP cell line compared with the parental A549 cell line by RNA sequencing. The knockdown of GPX2 expression in A549/DDP cells inhibited cell proliferation in vitro and in vivo, decreased the IC50 values of DDP, induced apoptosis, inhibited the activities of GSH-Px and superoxide dismutase (SOD), inhibited ATP production and glucose uptake, and increased malondialdehyde (MDA) and reactive oxygen species (ROS) production; while GPX2 overexpression in A549 cells resulted in the opposite effects. Using gene set enrichment analysis (GSEA), we found that GPX2 may be involved in DDP resistance through mediating drug metabolism, the cell cycle, DNA repair and energy metabolism, and the regulation of an ATP-binding cassette (ABC) transporters member ABCB6, which is one of the hallmark genes in glycolysis. Moreover, immunohistochemistry revealed that GPX2 was upregulated in 58.6% (89/152) of LUAD cases, and elevated GPX2 expression was correlated with high expression of ABCB6, high 18-fluorodeoxyglucose (18F-FDG) uptake, and adverse disease-free survival (DFS) in our cohort. The Cancer Genome Atlas (TCGA) data also indicated that GPX2 expression was higher in LUAD than it was in normal lung tissues, and the mRNA expression levels of GPX2 and ABCB6 were positively correlated. In conclusion, our study demonstrates that GPX2 acts as oncogene in LUAD and promotes DDP resistance by regulating oxidative stress and energy metabolism.

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Section: Lentivirus Infectionmentioning

confidence: 99%

“…Cisplatin (DDP) is a first-line chemotherapeutic DNA damage-inducing drug for lung cancer treatment. Currently, it is widely in use, despite new drugs being developed [2,3]. However, resistance to DDP has become a key obstacle in the effective treat-ment of patients with cancer [4].…”

Section: Introductionmentioning

confidence: 99%

Elevated Glutathione Peroxidase 2 Expression Promotes Cisplatin Resistance in Lung Adenocarcinoma

Jiao

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…The transition of immunotherapy from a theory to standard-of-care therapy has been driven by years of work. In particular, immune checkpoint inhibitor (ICI) therapies based on monoclonal antibodies have been proven to be remarkably effective [2].…”

Section: Introductionmentioning

confidence: 99%

Current status of the clinical use of PD-1/PD-L1 inhibitors: a questionnaire survey of oncologists in China

Zhang

Song

et al. 2020

BMC Cancer

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Background: The purpose of the present study was to obtain information on the use of PD-1/PD-L1 inhibitors by oncologists in China through a national questionnaire survey. Methods: Between the 7th and 25th of July in 2019, a questionnaire designed by the Chinese Society of Clinical Oncology Immuno-Oncology (CSCO IO) Committee on the current status of the use of PD-1/PD-L1 inhibitors was distributed online and offline to cancer-related medical departments in thirty different provinces and autonomous regions of China. The national questionnaire consisted of three sections as follows: general information, current status of the application of PD-1/PD-L1 inhibitors in the clinic, and oncologists' concerns regarding utilization. Results: The valid response rate of the current status survey was 76.3%. The proportion of senior doctors (physician-in-charge or a more superior position for more than 3 years) among the respondents was relatively high (67.0% in 588). Of the respondents, 59.2% had prescribed PD-1/PD-L1 inhibitors during clinical treatment, and the most frequent reason for not prescribing these inhibitors was the choice "do not understand the mechanism and the efficacy of PD-1/PD-L1 inhibitors". In addition, 77.9% of the prescribers used the medications in an off-label situation, and the most important motivation for this use was the fact that "there were indications abroad but not domestically". In addition, 77.9% of the prescribers believed that "immunotherapy-related adverse effects could be controlled or intervened through follow-up management". The prescribers were mostly concerned about "how to identify pseudoprogression and hyperprogression" and "immunity-related adverse effects management". Conclusion: The present study highlights the current status of PD-1/PD-L1 inhibitors in China. Increasing numbers of medical oncologists are interested in PD-1/PD-L1 inhibitors, and they are in need of immunotherapy education.

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“…In various types of cancer like lung cancer and biliary tract cancer, the combination also seems to be superior compared to single immunotherapy or chemotherapy alone. [157][158][159][160]. Additionally, for pancreatic cancer the combination of gemcitabine chemotherapy with PD1 was well tolerated and holds promise [161].…”

Section: Chemotherapymentioning

confidence: 99%

Opportunities for Conventional and In Situ Cancer Vaccine Strategies and Combination with Immunotherapy for Gastrointestinal Cancers, A Review

Bouzid

Peppelenbosch

Buschow

2020

Cancers

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Survival of gastrointestinal cancer remains dismal, especially for metastasized disease. For various cancers, especially melanoma and lung cancer, immunotherapy has been proven to confer survival benefits, but results for gastrointestinal cancer have been disappointing. Hence, there is substantial interest in exploring the usefulness of adaptive immune system education with respect to anti-cancer responses though vaccination. Encouragingly, even fairly non-specific approaches to vaccination and immune system stimulation, involving for instance influenza vaccines, have shown promising results, eliciting hopes that selection of specific antigens for vaccination may prove useful for at least a subset of gastrointestinal cancers. It is widely recognized that immune recognition and initiation of responses are hampered by a lack of T cell help, or by suppressive cancer-associated factors. In this review we will discuss the hurdles that limit efficacy of conventional cancer therapeutic vaccination methods (e.g., peptide vaccines, dendritic cell vaccination). In addition, we will outline other forms of treatment (e.g., radiotherapy, chemotherapy, oncolytic viruses) that also cause the release of antigens through immunogenic tumor cell death and can thus be considered unconventional vaccination methods (i.e., in situ vaccination). Finally, we focus on the potential additive value that vaccination strategies may have for improving the effect immunotherapy. Overall, a picture will emerge that although the field has made substantial progress, successful immunotherapy through the combination with cancer antigen vaccination, including that for gastrointestinal cancers, is still in its infancy, prompting further intensification of the research effort in this respect.

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Effectiveness and safety of PD-1/PD-L1 or CTLA4 inhibitors combined with chemotherapy as a first-line treatment for lung cancer: A meta-analysis

Cited by 36 publications

References 52 publications

Elevated Glutathione Peroxidase 2 Expression Promotes Cisplatin Resistance in Lung Adenocarcinoma

Elevated Glutathione Peroxidase 2 Expression Promotes Cisplatin Resistance in Lung Adenocarcinoma

Current status of the clinical use of PD-1/PD-L1 inhibitors: a questionnaire survey of oncologists in China

Opportunities for Conventional and In Situ Cancer Vaccine Strategies and Combination with Immunotherapy for Gastrointestinal Cancers, A Review

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