Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1/2-AP-1 signaling pathway

Tsai, Te‐Fu; Lin, Jennifer; Lin, Yi‐Chia; Chou, Kan‐Sen; Chen, Hung-En; Ho, Chao‐Yen; Chen, Po-Chun; Hwang, Thomas I‐Sheng

doi:10.1042/bsr20190362

Cited by 46 publications

(35 citation statements)

References 29 publications

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“…However, in our cohort, a high proportion of UC CKD patients, 54.4%, still received cisplatin-based chemotherapy. Preclinical data support a synergism between cisplatin and PD-L1 blockade through enhanced T cell responses and PD-L1 expression on tumor cells [ 34 , 35 ]. Larger cohorts of patients with CKD and CPI treatment are needed to confirm this result.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study

Seydel

Delecluse

Zeier

et al. 2021

Cancers

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Background: Checkpoint inhibitors are a standard of care in the treatment of advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC). Patients with these tumors often suffer from concomitant chronic kidney disease (CKD). Limited data are available on the efficacy and toxicity of checkpoint inhibitors in patients with CKD. Methods: We retrospectively analyzed 126 patients who received checkpoint inhibitors for RCC (n = 85) or UC (n = 41) and analyzed the frequency of treatment- and immune-related adverse events (AEs). We performed a multivariate analysis to determine progression-free survival (PFS) and overall survival (OS). Results: A total of 38.9% of patients had CKD. Frequencies of general AEs (49.0% in CKD vs. 48.1%, p > 0.99999) and immune-related AEs (28.6 vs. 24.7%, p ≥ 0.9999) did not significantly differ between the groups. There was no difference in PFS for patients with RCC or UC and CKD or without CKD (RCC: 6.81 vs. 7.54 months, HR 1.000 (95%CI 0.548-01.822), p = 0.999; UC:2.33 vs. 3.67 months, HR 01.492 (95%CI 0.686-3.247), p = 0.431). CKD appeared to be a potential effect modifier for OS in both RCC and UC (RCC: NR vs. 23.9 months, HR 0.502 (95%CI 0.219-1.152), p = 0.104; UC:18.84 vs. 15.42 months, HR 0.656 (95%CI 0.296-1.454), p = 0.299). Conclusions: Checkpoint inhibitor treatment in our cohort of patients with CKD was as safe and efficient as in the cohort of patients without CKD.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study

Seydel

Delecluse

Zeier

et al. 2021

Cancers

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“…In bladder cancer cell lines, cisplatin is able to induce the expression of PD-L1 in vitro [127]. The combination of cisplatin and anti-PD-L1 is also synergic in murine thymoma.…”

Section: Platinum Derivatives and Immune Checkpointsmentioning

confidence: 99%

Platinum Derivatives Effects on Anticancer Immune Response

et al. 2019

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Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells' fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints' expression.Cell death is characterized by morphological alterations that have been historically used by The Nomenclature Committee on Cell Death (NCCD) to classify this cellular process into three different forms: type I or apoptosis, type II or autophagy, and type III or necrosis. Although limited, this morphological classification remains widely used, independently of essential molecular aspects of the cell death process. New NCCD classifications focus on molecular mechanisms and on the biochemistry of intracellular signalization effectors. Currently, it is clear that connections and overlaps exist between the different types of cell death. The majority of chemotherapeutic drugs are known to induce apoptosis or necrosis. Engagement of a particular type of cell death depends on the stress type, interaction between induction factors, genetic cell background, organelle content and enzymatic proteins arsenal [3,4].The action of chemotherapy relies not only on its cytotoxic effect on cancer cells, but also on its ability to affect immune cells.

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“…It has recently been reported that cisplatin induces PD‐L1 expression in bladder cancer and non–small cell lung cancer cell lines . In bladder cancer, cisplatin treatment serves to upregulate PD‐L1 expression via the ERK signaling pathway, followed by AP‐1.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have evaluated the ability of chemotherapy, including anti–tumor drugs such as cisplatin, to modulate tumor immunogenicity and to influence adaptive immunity . From these studies, it has recently been reported that cisplatin induces the expression of PD‐L1 in bladder cancer and non–small cell lung cancer . However, the expression and regulatory mechanisms of PD‐L2 have not been evaluated in OSCC.…”

Section: Introductionmentioning

confidence: 99%

Cisplatin‐induced programmed cell death ligand‐2 expression is associated with metastasis ability in oral squamous cell carcinoma

et al. 2020

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Programmed cell death ligands (PD-Ls) are expressed in tumor cells where they bind to programmed cell death-1, an immunocyte co-receptor, resulting in tumor cell evasion from the immune system. Chemotherapeutic drugs have been recently reported to induce the expression of PD-L, such as PD-L1, in some cancer cells. However, little is known regarding PD-L2 expression and its role in oral squamous cell carcinoma (OSCC). In this study, we examined the effect of cisplatin on the expression and regulation of PD-L2 in OSCC cell lines and analyzed malignant behavior in PD-L2-expressing cells using colony, transwell and transformation assays. In addition, we examined PD-L2 expression in the tumor tissues of OSCC patients using cytology and tissue microarray methods. In OSCC cell lines, cisplatin treatment upregulated PD-L2 expression, along with that of the drug efflux transporter ABCG2, via signal transducers and activator of transcription (STAT) 1/3 activation. Moreover, PD-L2positive or PD-L2-overexpressing cells demonstrated upregulation in both invasion and transformation ability but not in proliferation compared with PD-L2-negative or PD-L2-silencing cells. PD-L2 expression was also observed in OSCC cells of cytology samples and tissue from OSCC patients. The intensity of PD-L2 expression was correlated with more malignant morphological features in the histological appearance and an invasive pattern. Our findings indicate that cisplatin-upregulated PD-L2 expression in OSCC via STAT1/3 activation and the expression of PD-L2 are likely to be associated with malignancy in OSCC. The PD-L2 expression in cisplatin-resistant OSCC cells may be a critical factor in prognosis of advanced OSCC patients.

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Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1/2-AP-1 signaling pathway

Cited by 46 publications

References 29 publications

Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study

Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study

Platinum Derivatives Effects on Anticancer Immune Response

Cisplatin‐induced programmed cell death ligand‐2 expression is associated with metastasis ability in oral squamous cell carcinoma

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