From Clinical Trials to Real-life Clinical Practice: The Role of Immunotherapy with PD-1/PD-L1 Inhibitors in Advanced Urothelial Carcinoma

Hussain, Syed A.; Birtle, Alison; Crabb, Simon J.; Huddart, Robert; Small, Diane; Summerhayes, M.; Jones, Robert J.; Protheroe, Andrew

doi:10.1016/j.euo.2018.05.011

Cited by 42 publications

(34 citation statements)

References 36 publications

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“…Therefore, PDL1 was an important anti-tumor therapeutic target due to it was expressed in most cancer cells. The drugs or antibodies targeting PDL1 were the promising therapeutic strategies in various types of cancer, which is being tested in clinical trials for multiple tumors (Hussain, Birtle et al, 2018;Wang, Zhou et al, 2019). Surely, a limited sample size, with only 26 samples were evaluated during the study, which might lead to un-objective conclusions.…”

Section: Discussionmentioning

confidence: 99%

circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis

Jiang

Hou

Liu

et al. 2021

J Pharmacol Exp Ther

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Background: Recently, circular RNA (circRNA) was reported to be a significant participant in the development of tumorigenesis, including colorectal cancer. Therefore, we aimed to clarify the precise role of circ-keratin 6C (circ-KRT6C) in colorectal cancer progression. Methods: The relative expression levels of circ-KRT6C, microRNA-16-5p (miR-485-3p), and programmed cell death receptor ligand 1 (PDL1) were analyzed by real-time quantitative polymerase chain reaction and western blot assays. The proliferation was assessed by cell count kit 8 and colony-forming assays. The apoptotic cells were determined by flow cytometry assay. The migration and invasion were analyzed by transwell assay. Colorectal cancer cells were co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells to assess immune response. The interaction relationships among circ-KRT6C, miR-485-3p, and PDL1 were examined by dual-luciferase reporter assay. The effects of circ-KRT6C inhibition in vivo was analyzed by an animal experiment. Results: Circ-KRT6C was overexpressed in colorectal cancer tissues and cells, and its level was associated with overall survival time of colorectal cancer patients. The suppression of circ-KRT6C suppressed growth, migration, invasion, and immune escape while stimulated apoptosis in colorectal cancer cells, which was abolished by shortage of miR-485-3p. In addition, overexpression of miR-485-3p repressed malignant progression and immune evasion of colorectal cancer by targeting PDL1, implying that PDL1 was a functional target of miR-485-3p. A xenograft experiment also suggested that circ-KRT6C inhibition could repress tumor growth in vivo. Conclusion: Circ-KRT6C could increase PDL1 expression by functioning as a miR-485-3p sponge, which promoted malignant progression and immune evasion of colorectal cancer cells.

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Section: Discussionmentioning

confidence: 99%

circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis

Jiang

Hou

Liu

et al. 2021

J Pharmacol Exp Ther

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“…The clinical application of PD-1/PD-L1 related immunotherapies implies the potential immunogenicity of bladder cancer (5,25). However, PD-1/PD-L1 related immunotherapy for bladder cancer, especially for patients with MIBC, is still improvable (5), as these are effective in only a certain proportion of patients with bladder cancer (26). Some patients with MIBC undergoing PD-1 related therapies have progressed to develop hyper-progressive disease (8).…”

Section: Discussionmentioning

confidence: 99%

PD-1-Positive Tumor-Associated Macrophages Define Poor Clinical Outcomes in Patients With Muscle Invasive Bladder Cancer Through Potential CD68/PD-1 Complex Interactions

et al. 2021

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Tumor-associated macrophages (TAMs) regulate tumor immunity. Previous studies have shown that the programmed cell death protein 1 (PD-1)-positive TAMs have an M2 macrophage phenotype. CD68 is a biomarker of TAMs and is considered to be a poor prognostic marker of several malignancies. Our results show that PD-1-positive TAMs can be a negative survival indicator in patients with muscle-invasive bladder cancer (MIBC), and that the mechanistic effects could result due to a combination of PD-1 and CD68 activity. We analyzed 22 immune cell types using data from 402 patients with MIBC from the TCGA database, and found that a high immune score and M2 TAMs were strongly associated with poor clinical outcomes in patients with MIBC. Further, we analyzed resected samples from 120 patients with MIBC and found that individuals with PD-1-positive TAMs showed a reduction in 5-year overall survival and disease-free survival. Additionally, PD-1-positive TAMs showed a significant association with higher programmed death-ligand 1 (PD-L1) expression, the Ki67 index, the pT stage and fewer CD8-positive T cells. Through the co-immunoprecipitation (co-IP) assay of THP-1 derived macrophages, we found that CD68 can bind to PD-1. The binding of CD68 and PD-1 can induce M2 polarization of THP-1 derived macrophages and promote cancer growth. The anti-CD68 treatment combined with peripheral blood mononuclear cells (PBMC) showed obvious synergy effects on inhibiting the proliferation of T24 cells. Together, these results indicate for the first time that CD68/PD-1 may be a novel target for the prognosis of patients with MIBC.

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“…On the other hand, the decrease in post-treatment PD-L1 expression was also observed and, in such patients, anti-PD-L1/PD-1 therapy following BCG failure might be limited [8]. Notwithstanding, it should be emphasised that patients with negative PD-L1 expression could also benefit from checkpoint immunotherapy [12]. Therefore, further clinical trials should be conducted to precisely elucidate the utility of PD-L1 expression as a predictor of checkpoint inhibitors response in patients with failure of BCG therapy.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of programmed cell death protein ligand 1 in patients with non-muscle-invasive bladder cancer treated with bacille Calmette–Guérin immunotherapy: Current status

Nowak

Krajewski

Poterek

et al. 2020

Arab Journal of Urology

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From Clinical Trials to Real-life Clinical Practice: The Role of Immunotherapy with PD-1/PD-L1 Inhibitors in Advanced Urothelial Carcinoma

Cited by 42 publications

References 36 publications

circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis

circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis

PD-1-Positive Tumor-Associated Macrophages Define Poor Clinical Outcomes in Patients With Muscle Invasive Bladder Cancer Through Potential CD68/PD-1 Complex Interactions

The prognostic value of programmed cell death protein ligand 1 in patients with non-muscle-invasive bladder cancer treated with bacille Calmette–Guérin immunotherapy: Current status

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