Relationship of Metabolic Alterations and PD-L1 Expression in Cisplatin Resistant Lung Cancer

Wangpaichitr, Medhi; Kandemir, Hande; Li, Y Y; Wu, Chunjing; Nguyen, Djm; Feun, Lynn G.; Kuo, M. Tien; Savaraj, Niramol

doi:10.4172/2168-9296.1000183

Cited by 25 publications

(16 citation statements)

References 66 publications

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“…This complex relationship between EMT and PD-L1 signaling plays an important role in the immune evasion of the tumors [80]. On the other hand, these findings may suggest that cisplatin-resistant EMT tumor cells could display an increased sensitivity to anti-PD-1 or anti-PD-L1 antibody treatment [82]. However, recent studies investigating gene expression signatures, predicting the efficacy of PD-1/PD-L1 inhibitors in different cancer types, found that tumors with EMT or the mesenchymal phenotype showed a lower response rate [83][84][85].…”

Section: Interaction With An Inflammatory Microenvironmentmentioning

confidence: 99%

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Dudás

Ladányi

Ingruber

et al. 2020

Cells

138

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Epithelial to mesenchymal transition (EMT) contributes to tumor progression, cancer cell invasion, and therapy resistance. EMT is regulated by transcription factors such as the protein products of the SNAI gene family, which inhibits the expression of epithelial genes. Several signaling pathways, such as TGF-beta1, IL-6, Akt, and Erk1/2, trigger EMT responses. Besides regulatory transcription factors, RNA molecules without protein translation, micro RNAs, and long non-coding RNAs also assist in the initialization of the EMT gene cluster. A challenging novel aspect of EMT research is the investigation of the interplay between tumor microenvironments and EMT. Several microenvironmental factors, including fibroblasts and myofibroblasts, as well as inflammatory, immune, and endothelial cells, induce EMT in tumor cells. EMT tumor cells change their adverse microenvironment into a tumor friendly neighborhood, loaded with stromal regulatory T cells, exhausted CD8+ T cells, and M2 (protumor) macrophages. Several EMT inhibitory mechanisms are instrumental in reversing EMT or targeting EMT cells. Currently, these mechanisms are also significant for clinical use.

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Section: Interaction With An Inflammatory Microenvironmentmentioning

confidence: 99%

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Dudás

Ladányi

Ingruber

et al. 2020

Cells

138

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“…Cisplatin resistant ovarian cancer cells have an active glutathione (GSH) synthesis pathway and high level of intracellular GSH ( Table 1 ), suggesting that an increase of cellular GSH is a beneficial mechanism to cope with cisplatin induced oxidative stress [ 21 , 32 ]. For example, cisplatin resistant lung cancer cells increase ROS production through metabolic reprogramming and become more dependent on oxidative metabolism rather than glycolysis [ 35 , 36 , 37 ]. High levels of ROS and other metabolic alterations promote EMT [ 36 ].…”

Section: Metabolic Reprogramming Contributes To Chemoresistancementioning

confidence: 99%

“…For example, cisplatin resistant lung cancer cells increase ROS production through metabolic reprogramming and become more dependent on oxidative metabolism rather than glycolysis [ 35 , 36 , 37 ]. High levels of ROS and other metabolic alterations promote EMT [ 36 ]. These cells take up more glutamine and are highly sensitive to glutamine deprivation.…”

Section: Metabolic Reprogramming Contributes To Chemoresistancementioning

confidence: 99%

Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential Significance of Metabolic Regulation in the Reversal of Cancer Chemoresistance

Chen

2020

Metabolites

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Metabolic reprogramming is one of the hallmarks of tumors. Alterations of cellular metabolism not only contribute to tumor development, but also mediate the resistance of tumor cells to antitumor drugs. The metabolic response of tumor cells to various chemotherapy drugs can be analyzed by metabolomics. Although cancer cells have experienced metabolic reprogramming, the metabolism of drug resistant cancer cells has been further modified. Metabolic adaptations of drug resistant cells to chemotherapeutics involve redox, lipid metabolism, bioenergetics, glycolysis, polyamine synthesis and so on. The proposed metabolic mechanisms of drug resistance include the increase of glucose and glutamine demand, active pathways of glutaminolysis and glycolysis, promotion of NADPH from the pentose phosphate pathway, adaptive mitochondrial reprogramming, activation of fatty acid oxidation, and up-regulation of ornithine decarboxylase for polyamine production. Several genes are associated with metabolic reprogramming and drug resistance. Intervening regulatory points described above or targeting key genes in several important metabolic pathways may restore cell sensitivity to chemotherapy. This paper reviews the metabolic changes of tumor cells during the development of chemoresistance and discusses the potential of reversing chemoresistance by metabolic regulation.

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“…Specifically, signaling through PDL1 was found to directly upregulate glycolysis in tumor cells through activating the AKT/mTOR pathway ( 43 ), leading to enhanced glucose uptake and lactate production and the expansion and survival of these tumor cells. Conversely, a therapeutic inhibitor of PDL1 decreased the glycolysis rate via blocking interactions between PDL1 and the PD1 receptor, restoring glucose levels in tumor cells and limiting tumor progression ( 50 , 51 ). Other immune checkpoint inhibitors, such as CD47, inhibit the phagocytosis of cancer cells by binding to the signal regulatory protein α (SIRPα) receptor expressed on macrophages and DCs ( 52 , 53 ).…”

Section: Immune Checkpoint Inhibitors and Mitochondrial Metabolismmentioning

confidence: 99%

Role of Mitochondria in Cancer Immune Evasion and Potential Therapeutic Approaches

Klein

Younes

et al. 2020

Front. Immunol.

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The role of mitochondria in cancer formation and progression has been studied extensively, but much remains to be understood about this complex relationship. Mitochondria regulate many processes that are known to be altered in cancer cells, from metabolism to oxidative stress to apoptosis. Here, we review the evolving understanding of the role of mitochondria in cancer cells, and highlight key evidence supporting the role of mitochondria in cancer immune evasion and the effects of mitochondria-targeted antitumor therapy. Also considered is how knowledge of the role of mitochondria in cancer can be used to design and improve cancer therapies, particularly immunotherapy and radiation therapy. We further offer critical insights into the mechanisms by which mitochondria influence tumor immune responses, not only in cancer cells but also in immune cells. Given the central role of mitochondria in the complex interactions between cancer and the immune system, high priority should be placed on developing rational strategies to address mitochondria as potential targets in future preclinical and clinical studies. We believe that targeting mitochondria may provide additional opportunities in the development of novel antitumor therapeutics.

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Relationship of Metabolic Alterations and PD-L1 Expression in Cisplatin Resistant Lung Cancer

Cited by 25 publications

References 66 publications

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential Significance of Metabolic Regulation in the Reversal of Cancer Chemoresistance

Role of Mitochondria in Cancer Immune Evasion and Potential Therapeutic Approaches

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