Targeting PD-L1 for Non-Small-Cell Lung Cancer

Feld, Emily; Horn, Leora

doi:10.2217/imt-2016-0012

Cited by 13 publications

(13 citation statements)

References 52 publications

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“…A series of immunotherapeutic approaches, including anti-PD-1 therapy and anti-PD-L1 therapy, had previously been established for NSCLC (7,32). In this study, our results showed that SIRPaD1-Fc therapy could elicit potent anti-NSCLC efficacy in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 58%

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non–Small Cell Lung Cancer

Zhang

Fan

Wang

et al. 2017

Cancer Immunology Research

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CD47-specific antibodies and fusion proteins that block CD47-SIRPa signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in nonsmall cell lung cancer (NSCLC). SIRPaD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Meanwhile, reactive oxygen species and inactivation of mTOR were shown to be involved in autophagy initiation in SIRPaD1-Fc-treated cells, indicating a probable mechanism for autophagy activation after targeting CD47 by SIRPaD1-Fc. Inhibition of autophagy enhanced macrophage-mediated phagocytosis and cytotoxicity against SIRPaD1-Fc-treated NSCLC cells. In addition, simultaneously targeting both CD47 and autophagy in NSCLC xenograft models elicited enhanced antitumor effects, with recruitment of macrophages, activated caspase-3, and overproduction of ROS at the tumor site. Our data elucidated the cytoprotective role of autophagy in CD47-targeted therapy and highlighted the potential approach for NSCLC treatment by simultaneously targeting CD47 and autophagy.

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Section: Discussionmentioning

confidence: 58%

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non–Small Cell Lung Cancer

Zhang

Fan

Wang

et al. 2017

Cancer Immunology Research

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“…PD-L1 expression was also detected on the cell surfaces of numerous types of cancer, including bladder, kidney, ovarian, lung, and melanoma, which was associated with poorer immune response and worse prognosis for patients. The large amounts of PD-L1 help some cancer cells to hide from an immune attack (Feld et al, 2016;Lee et al, 2016;Maleki et al, 2017;Xiang et al, 2017;Rom-Jurek et al, 2018). The presence of this protein has been also demonstrated in colorectal carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Mechanisms of Tumor Cell Immunoresistance

et al. 2020

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One of the main mechanisms for avoiding immune response by cancer cells is by inducing an immunosuppressive environment in the tumor, following the activation of immune checkpoints i.e. PD-1 or CTLA-4 receptor inhibitors on T lymphocytes. Inhibiting the interaction between PD-1 or CTLA-4 and their ligands (PD-L1, CD80, and CD85) leads to unblocking T-lymphocyte function, and thus destroying cancer cells. Certain intracellular signaling pathways are also involved in the development of tumor cell immunoresistance. Blocking the activation of immunosuppressive pathways may increase immunological anti-tumor control

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“…Lung cancer, one of the most frequently diagnosed cancers, has become the leading cause of cancer‐related death worldwide . According to Global Cancer Statistics 2018, lung cancer is responsible for approximately 2.09 million newly diagnosed cancer cases and 1.76 million cancer‐related deaths worldwide .…”

Section: Introductionmentioning

confidence: 99%

“…During the past two decades, some advancements in the treatments of NSCLC have been achieved, such as the application of small molecule tyrosine kinase inhibitors and immunotherapy, which benefit to some selected patients . Nevertheless, the prognosis of NSCLC patients (especially those with metastasis disease) is still dismal, with a 5‐year survival rate of just 15% . Hence, continued research into more effective screening for predicting disease progression in NSCLC patients at an early stage is required, and with this aim, molecular markers may expand the screening approach to improve prognosis in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…Lung cancer, one of the most frequently diagnosed cancers, has become the leading cause of cancer-related death worldwide. 1,2 According to Global Cancer Statistics 2018, lung cancer is responsible for approximately 2.09 million newly diagnosed cancer cases and 1.76 million cancer-related deaths worldwide. 3 Non-small-cell lung cancer (NSCLC), which involves adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma, accounts for 85% of newly diagnosed lung cancers.…”

Section: Introductionmentioning

confidence: 99%

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A‐kinase‐interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles, and promotes cell proliferation but represses apoptosis in non‐small‐cell lung cancer

Chen

Yan

Liu

et al. 2019

Clinical Laboratory Analysis

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Background This study aimed to explore the correlation of A‐kinase‐interacting protein 1 (AKIP1) expression with clinical characteristics as well as survival profiles in non‐small‐cell lung cancer (NSCLC) patients, and further investigate its underlying effect on regulating NSCLC cell functions. Methods 319 NSCLC patients who underwent resection were consecutively reviewed, and AKIP1 expression (in 319 tumor tissues and 145 adjacent tissues) was determined by immunohistochemistry. Disease‐free survival (DFS) and overall survival (OS) were calculated. In vitro, control overexpression, AKIP1 overexpression, control shRNA and AKIP1 shRNA plasmids were transfected into A549 cells to evaluate the effect of AKIP1 on cell proliferation and apoptosis. Results A‐kinase‐interacting protein 1 expression was increased in tumor tissues compared to adjacent tissues, and it positively correlated with tumor size, lymph node metastasis and TNM stage in NSCLC patients. Kaplan‐Meier curves displayed that AKIP1 high expression correlated with worse DFS and OS, and multivariate Cox's regression revealed that it was an independent predictive factor for poor survival profiles. In vitro experiments displayed that AKIP1 expression was elevated in PC9 and A549 cells compared to normal lung epithelial cells; moreover, cell proliferation was increased by AKIP1 upregulation but reduced by AKIP1 downregulation, and cell apoptosis was decreased by AKIP1 upregulation but increased by AKIP downregulation in A549 cells. Interestingly, AKIP1 promoted fibronectin and zinc finger E‐box binding homeobox 1 expressions while reduced E‐cadherin expression in A549 cells. Conclusion A‐kinase‐interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles and promotes cell proliferation but represses apoptosis in NSCLC.

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Targeting PD-L1 for Non-Small-Cell Lung Cancer

Cited by 13 publications

References 52 publications

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non–Small Cell Lung Cancer

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non–Small Cell Lung Cancer

Intracellular Mechanisms of Tumor Cell Immunoresistance

A‐kinase‐interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles, and promotes cell proliferation but represses apoptosis in non‐small‐cell lung cancer

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