Adverse Events of Immune Checkpoint Inhibitors Therapy for Urologic Cancer Patients in Clinical Trials: A Collaborative Systematic Review and Meta-analysis

Wu, Zhenjie; Chen, Qi; Qu, Le; Li, Mingmin; Wang, Linhui; Mir, M.C.; Carbonara, Umberto; Pandolfo, Savio Domenico; Black, Peter C.; Paul, Asit K.; Lorenzo, Giuseppe Di; Porpiglia, Francesco; Mari, Andrea; Necchi, Andrea; Rouprêt, Morgan; Psutka, Sarah P.; Autorino, Riccardo

doi:10.1016/j.eururo.2022.01.028

Cited by 54 publications

(42 citation statements)

References 62 publications

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“…Tumor-infiltrating immune cells are a crucial element in the tumor microenvironment and have been found to influence proliferation, invasion, and metastasis in various cancer types ( Bremnes et al, 2016 ; Xiong et al, 2019b ; Yang et al, 2020 ). Tumor-infiltrating immune cells and immune checkpoints are thought to play an essential role in immunotherapy, making them hotspot studies in ccRCC treatment ( Xu et al, 2021 ; Wu et al, 2022 ). Our results revealed a clear correlation between NCKAP1 levels and immune cell counts and biomarker levels.…”

Section: Discussionmentioning

confidence: 99%

NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma

Chen

Zhang

et al. 2022

Front. Genet.

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Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. Nck-associated protein 1 (NCKAP1) is associated with poor prognosis and tumor progression in several cancer types, but the function and prognostic value of NCKAP1 in ccRCC remain poorly understood.Methods: Using the Ualcan database, we evaluated the correlation between NCKAP1 expression and clinical features of ccRCC. These data were validated by immunohistochemical staining for NCKAP1 in a cohort of ccRCC patients. We assessed the prognostic value of NCKAP1 using GEPIA2 survival analysis. NCKAP1 function was characterized in vitro and in vivo using NCKAP1-overexpression ACHN cell lines. The LinkedOmics and GSCALite databases were used to investigate identify potential NCKAP1-targeted medicines that may play a role in the treatment of ccRCC. The impact of NCKAP1 expression on immune infiltration was also evaluated.Results: NCKAP1 was significantly downregulated in ccRCC and correlated with advanced clinicopathological features and poor prognosis. Overexpression of NCKAP1 in ACHN cells reduced proliferation, invasion and migration capacity in vitro and inhibited tumor growth in vivo. According to the LinkedOmics, GSCALite and TIMER databases, NCKAP1 and related genes function primarily in ribosomal signaling, oxidative phosphorylation, TGF-β, and EMT-related signaling pathways. NCKAP1 was also shown to positively correlate with immune cell types, biomarkers, and immune checkpoints in ccRCCs.Conclusions: NCKAP1 may play a vital tumor-suppressive role in ccRCC and is potentially a useful prognostic biomarker.

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Section: Discussionmentioning

confidence: 99%

NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma

Chen

Zhang

et al. 2022

Front. Genet.

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“…The highest incidence of irAEs has been reported for the nivolumab plus ipilimumab combination with 33% Grade 3–4 irAEs in the CheckMate-227 trial [ 8 ] as compared with the 19% incidence in the nivolumab arm. Such a higher rate of severe irAEs was also reported in the meta-analysis of urological cancers ICI trials [ 9 ], which also identified the length of exposure to ICI as a variable associated with an increased incidence of severe irAEs [ 9 ], although most of the irAEs occur within the first months of treatment [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 56%

Grade 3–4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study

Guezour

Soussi

Brosseau

et al. 2022

Cancers

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Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3–4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3–4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7–13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2–0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC.

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“…According to the latest research by Wu et al. ( 34 ), the adverse events of immune checkpoint inhibitor therapy for kidney cancer were significantly less reported than those in urothelial cancer or prostate cancer, proposing the full-fledged rather than experimental roles of ICB therapies in RCC. Beuselinck et al.…”

Section: Discussionmentioning

confidence: 99%

Integrated Multi-Omics Analysis Identified PTPRG and CHL1 as Key Regulators of Immunophenotypes in Clear Cell Renal Cell Carcinoma(ccRCC)

Zeng

et al. 2022

Front. Oncol.

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Despite the increasing importance and status of immune checkpoint blockade (ICB), little is known about the underlying molecular mechanisms determining the target clear cell renal cell carcinoma (ccRCC) population. In this study, we screened out 6 immune cells strongly correlated with expression levels of PD-L1 and IFN-γ based on the ccRCC samples extracted from GSE and TCGA data sets. By performing unsupervised clustering and lasso regression analysis, we grouped the ccRCC into 4 clusters and selected the two most distinct sub-clusters for further investigation—cluster A1 and B1. Next, we compared the two clusters in terms of mRNA, somatic mutations, copy number variations, DNA methylation, miRNA, lncRNA and constructed the differentially expressed genes (DEGs) hub by combing together the previous results at levels of DNA methylation, miRNA, and lncRNA. PTPRG and CHL1 were identified as key nodes in the regulation hub of immunophenotypes in ccRCC patients. Finally, we established the prognosis model by using Lasso-Cox regression and Kaplan–Meier analysis, recognizing WNT2, C17orf66, and PAEP as independent significant risk factors while IRF4 as an independent protective factor.

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Adverse Events of Immune Checkpoint Inhibitors Therapy for Urologic Cancer Patients in Clinical Trials: A Collaborative Systematic Review and Meta-analysis

Cited by 54 publications

References 62 publications

NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma

NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma

Grade 3–4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study

Integrated Multi-Omics Analysis Identified PTPRG and CHL1 as Key Regulators of Immunophenotypes in Clear Cell Renal Cell Carcinoma(ccRCC)

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