PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies

Ding, Lei; Dong, Hongyan; Zhou, Tian Ren; Wang, Yu Hao; Yan, Tao; Li, Jun Chen; Wang, Zhong Yuan; Li, Jie; Liang, Chao

doi:10.1002/cam4.4190

Cited by 13 publications

(8 citation statements)

References 143 publications

(184 reference statements)

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“…ccRCC is reported to be a malignancy with high immunogenicity, which has been proven infiltrated by a large amount of immunocytes, including macrophage, NK cells, and T cells (32,33). Especially, the disrupting activation of antigen presentation and the ruin of the immune system were impacted by the abnormal transformation of dendritic cells and the inactivation of T cells (34,35). Several studies illustrated that the abundance of tumor-infiltrating lymphocytes and CD8+ T cells is inversely correlated with the prognosis of ccRCC patients (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical Outcome via Effecting Tumor Immunity for ccRCC, Is Related to Cell Invasion, Metastasis, and Sunitinib Sensitivity

et al. 2022

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Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma and is associated with poor prognosis and notorious for its immune dysfunction characteristic. SNRPA1 is a spliceosome component responsible for processing pre-mRNA into mRNA, while the biological effect of SNRPA1 in ccRCC remains elusive. The aim of this study was to decipher the effect of SNRPA1 on clinical effect and tumor immunity for ccRCC patients. Multi-databases were collected to evaluate the different expression, prognostic value, DNA methylation, tumor immune microenvironment, and drug sensitivity of SNRPA1 on ccRCC. IHC was utilized to validate the expression and prognostic value of SNRPA1 in ccRCC patients from the SMMU cohort. The knockout expression of SNRPA by sgRNA plasmid inhibited the cell proliferation, migration, and metastasis ability and significantly increased the sensitivity of sunitinib treatment. In addition, we explored the role of SNRPA1 in pan-cancer level. The results indicated that SNRPA1 was differentially expressed in most cancer types. SNRPA1 may significantly influence the prognosis of multiple cancer types, especially in ccRCC patients. Notably, SNRPA1 was significantly correlated with immune cell infiltration and immune checkpoint inhibitory genes. In addition, the aggressive and immune inhibitory effects shown in SNRPA1 overexpression and the effect of SNRPA1 on ccRCC cell line invasion, metastasis, and drug sensitivity in vitro were observed. Moreover, SNRPA1 was related to Myc, MTORC, G2M, E2F, and DNA repair pathways in various cancer types. In all, SNRPA1 may prove to be a new biomarker for prognostic prediction, effect tumor immunity, and drug susceptibility in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical Outcome via Effecting Tumor Immunity for ccRCC, Is Related to Cell Invasion, Metastasis, and Sunitinib Sensitivity

et al. 2022

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“…However, for a tumour to develop from a newly formed cancerous cell, it must evolve mechanisms to evade the normal host immune response. One such mechanism is the expression of the surface proteins PD-L1 or PD-L2 and CD80/CD86 on the cancer cells that bind and activate the checkpoint proteins PD-1 and CTLA-4, respectively, on T cells [ 50 , 51 ]. This recognition halts target cell killing by CTLs and can even induce their apoptosis or differentiation into immunosuppressive T regulatory cells [ 50 , 51 ].…”

Section: Stinging Cancer: a New Class Of Immunotherapymentioning

confidence: 99%

“…One such mechanism is the expression of the surface proteins PD-L1 or PD-L2 and CD80/CD86 on the cancer cells that bind and activate the checkpoint proteins PD-1 and CTLA-4, respectively, on T cells [ 50 , 51 ]. This recognition halts target cell killing by CTLs and can even induce their apoptosis or differentiation into immunosuppressive T regulatory cells [ 50 , 51 ]. The development of checkpoint inhibitors, monoclonal antibodies that bind to and block the interactions of PD-1 and CTLA-4 with their cognate ligands, inhibits this interaction stimulating tumour clearing in a subset of patients [ 52 ].…”

Section: Stinging Cancer: a New Class Of Immunotherapymentioning

confidence: 99%

Au naturale: use of biologically derived cyclic di-nucleotides for cancer immunotherapy

Waters

2021

Open Biol.

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Cyclic di-nucleotides (CDNs) are widespread second messenger signalling molecules that regulate fundamental biological processes across the tree of life. These molecules are also potent modulators of the immune system, inducing a Type I interferon response upon binding to the eukaryotic receptor STING. Such a response in tumours induces potent immune anti-cancer responses and thus CDNs are being developed as a novel cancer immunotherapy. In this review, I will highlight the use, challenges and advantages of using naturally occurring CDNs to treat cancer.

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“…RCC cases with PD-L1 positive tumors have shorter survival than patients with tumors without PD-L1 expression [23,24]. Intrinsic factors such as genetic and epigenetic alterations, external factors such as some tumor microenvironment cytokines (such as IFN-γ), metabolic factors such as glucose disorders, and treatment methods can lead to the upregulation of PD-L1 in RCC cases [25].…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of combinational therapy (sorafenib and anti-miR-222) on renal cell carcinoma cell lines: an invitro study

Komijani

Delashoub

2023

Preprint

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Background: Sorafenib chemotherapy drug can fight renal cell carcinoma (RCC) cells, the most common kidney cancer, by preventing cell migration and viability and stimulating apoptosis. In recent years, studies on combination therapies in cancer have increased due to greater effectiveness and prevention of drug resistance. In this study, we aimed to investigate the apoptotic and anti-metastatic effect of sorafenib and anti-miR-222 on RCC cell lines Methods: 786-O and Caki-1 were used as RCC cell lines. Gene expression of PD-L1, Bim, miR-34a, miR-122, miR-513, and miR-570 were evaluated using quantitative real-time polymerase chain reaction(qRT-PCR) before and after sorafenib treatment. Changes in cell viability, apoptosis, and cell migration respectively were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, flow cytometry, and scratch assay after treatment of 786-O and Caki-1 cell lines with sorafenib and anti-miR-222. Results: Sorafenib led to increased expression of PD-L1, Bim, miR-34a, miR-122, miR-513, and miR-570genes in 786-O and Caki-1 cell lines. MTT assay results showed that cotreatment of 786-O and Caki-1 cell lines with sorafenib and anti-miR-222 solely and together decrease cell viability but combination therapies results were more significant. Also, the data of the apoptosis test showed an increased apoptosis rate in both 786-O and Caki-1 cell lines after treatment with sorafenib and anti-miR-222 solely and together but combination therapies results were more remarkable. The scratch test results also showed a decrease in cell migration in both cell lines in the treatment with sorafenib and anti-miR-222 solely and together after 24 and 48 hours but combination therapies results were more considerable. Conclusion: Therefore, the present study shows a significant enhancement of the increase in apoptosis, as well as a significant decrease in cell migration and viability, after the use of sorafenib and anti-miR-222 at the same time. It seems that these results can contribute to the development of therapeutic strategies against RCC.

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PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 143 publications

Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical Outcome via Effecting Tumor Immunity for ccRCC, Is Related to Cell Invasion, Metastasis, and Sunitinib Sensitivity

Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical Outcome via Effecting Tumor Immunity for ccRCC, Is Related to Cell Invasion, Metastasis, and Sunitinib Sensitivity

Au naturale: use of biologically derived cyclic di-nucleotides for cancer immunotherapy

Anticancer effect of combinational therapy (sorafenib and anti-miR-222) on renal cell carcinoma cell lines: an invitro study

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