Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy

Zhu, Bo; Tang, Liming; Chen, Shuyang; Yin, Chengqian; Peng, Shichun; Li, Xin; Liu, Tongzheng; Liu, Wei; Han, Changpeng; Stawski, Lukasz; Xu, Zhixiang; Zhou, Guang‐Biao; Chen, Xiang; Gao, Xiumei; Goding, Colin R.; Xu, Nan; Cui, Rutao; Cao, Peng

doi:10.1038/s41388-018-0314-0

Cited by 93 publications

(75 citation statements)

References 54 publications

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“…Recently, it has been reported that Nrf2 and PD-L1 signaling pathway had co-regulatory functions in melanoma cancer. It has also been shown that NRF2 regulated PD-L1 expression, which can be considered as a potential alternative strategy for PD-1/PD-L1 antibody-based treatment of melanoma [22]. Up to now, the function of the Nrf2-PD-L1 axis has not been clari ed in the colon cancer especially in the oxaliplatin resistant cells.…”

Section: Discussionmentioning

confidence: 99%

“…We found a positive correlation between Nrf2 and PD-L1 mRNA expressions in tumor tissues. It has been shown that Nrf2 positively controlled PD-L1 expression [22].…”

Section: Discussionmentioning

confidence: 99%

“…Yin and colleagues conducted a study in 2018 that NRF2 is upstream of the PD-L1 regulator. NRF2 destruction or suppression signi cantly increased the activity of both CD4 + and CD8 + cells to inhibit the progression of melanoma; NRF2 inhibition in combination with anti-PD-1 therapy increased the anti-tumor e cacy [22]. Altogether, all of these studies clari ed that NRF2-targeted suppression has a strong rationale to be examined in cancer [23,24].…”

Section: Introductionmentioning

confidence: 91%

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The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells

Payandeh¹,

Tazehkand²,

Mansoori³

et al. 2020

Preprint

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Background: Nuclear factor−erythroid 2−related factor 2 (Nrf2) has a key function in promoting chemoresistance in various cancers. PD-L1 is one of the downstream targets of Nrf2 signaling pathway, having some beneficial impacts on tumors growth by inhibition of the immune system. The aim of this study was to investigate the potential role of Nrf2- PD- L1 axis in the promotion of oxaliplatin resistance in colon cancer cells. Result: Our data revealed that Nrf2 and PD-L1 mRNA expressions were markedly higher in tumor tissues compared to margin tissues. PD-L1 mRNA expression level was also increased in the resistant cells. However, Nrf2 expression was decreased and increased in SW480/Res and LS174T/Res cells, respectively. Nrf2 inhibition through siRNA in SW480/Res and LS174T/Res decreased the IC50 values of oxaliplatin. Inhibition of Nrf2 significantly increased oxaliplatin-induced apoptosis and reduced migration in SW480/Res cells when accompanied with oxaliplatin. Conclusion: Our study suggests that effective inhibition of Nrf2/PD-L1 signaling pathways can be considered as a novel approach to improve oxaliplatin efficacy in colon cancer patients.

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Section: Discussionmentioning

confidence: 99%

“…We found a positive correlation between Nrf2 and PD-L1 mRNA expressions in tumor tissues. It has been shown that Nrf2 positively controlled PD-L1 expression [22].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells

Payandeh¹,

Tazehkand²,

Mansoori³

et al. 2020

Preprint

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“…Nrf2/Keap1 is reported to be one of the signaling pathways involved in CRC initiation and progression (Jeddi, Soozangar, Sadeghi, Somi, & Samadi, 2017). Zhu et al (2018) have shown that Nrf2 functions as an upstream transcriptional activator of PD‐L1. However, various functions of Nrf2 in tumor formation and progression is still debatable.…”

Section: Introductionmentioning

confidence: 99%

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Payandeh

Khalili

Somi

et al. 2020

Journal Cellular Physiology

109

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Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.

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“…In addition, NRF-2 has been implicated in UV-induced expression of PD-L1 in melanoma. It has been shown that depletion of NRF-2 was associated with tumor infiltration by CD8+ and CD4+ T cells, whereas combined inhibition of NRF-2 and PD-1 demonstrated enhanced anti-melanoma effect [205]. This suggests that NRF-2 may also be considered as an alternative target to inhibit the PD-1/PD-L1 signaling.…”

Section: Ferroptosis In Melanomamentioning

confidence: 99%

Non-Apoptotic Cell Death Signaling Pathways in Melanoma

Hartman

2020

IJMS

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Resisting cell death is a hallmark of cancer. Disturbances in the execution of cell death programs promote carcinogenesis and survival of cancer cells under unfavorable conditions, including exposition to anti-cancer therapies. Specific modalities of regulated cell death (RCD) have been classified based on different criteria, including morphological features, biochemical alterations and immunological consequences. Although melanoma cells are broadly equipped with the anti-apoptotic machinery and recurrent genetic alterations in the components of the RAS/RAF/MEK/ERK signaling markedly contribute to the pro-survival phenotype of melanoma, the roles of autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and parthanatos have recently gained great interest. These signaling cascades are involved in melanoma cell response and resistance to the therapeutics used in the clinic, including inhibitors of BRAF mut and MEK1/2, and immunotherapy. In addition, the relationships between sensitivity to non-apoptotic cell death routes and specific cell phenotypes have been demonstrated, suggesting that plasticity of melanoma cells can be exploited to modulate response of these cells to different cell death stimuli. In this review, the current knowledge on the non-apoptotic cell death signaling pathways in melanoma cell biology and response to anti-cancer drugs has been discussed.

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Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy

Cited by 93 publications

References 54 publications

The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells

The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Non-Apoptotic Cell Death Signaling Pathways in Melanoma

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