Dynamics of Immune Checkpoints, Immune System, and BCG in the Treatment of Superficial Bladder Cancer

Saad, Farouk Tijjani; Hınçal, Evren; Kaymakamzade, Bilgen

doi:10.1155/2017/3573082

Cited by 13 publications

(6 citation statements)

References 28 publications

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“…These pathways are crucial for self-tolerance and innate immunity and prevent the immune system from attacking cells indiscriminately (2). Immune checkpoints consist of stimulatory checkpoint molecules and inhibitory checkpoint molecules (7,8). Inhibitory checkpoint molecules have been considered important targets for cancer immunotherapy (9).…”

Section: Introductionmentioning

confidence: 99%

PD‑L1 expression levels on tumor cells affect their immunosuppressive activity

Yang

Fang

2019

Oncol Lett

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Programmed cell death 1 (PD-1) is an immuno-checkpoint receptor which is primarily expressed on T cells, monocytes, natural killer cells and macrophages. Programmed death-ligand 1 (PD-L1) is the primary ligand of PD-1 and is constitutively expressed on antigen presenting cells, mesenchymal stem cells and bone marrow-derived mast cells. In addition, PD-L1 is also expressed on a wide range of tumor cells, including lung cancer, breast cancer and melanoma. PD-1 and PD-L1 are important members of the immunoglobulin super-family and participate in immune regulation. In the present study, the immune-suppressive effects of a number of tumor cell lines were determined. The breast tumor cell lines MCF-7 and MDA-MB-231 displayed the largest inhibitory effects on T-cell activation and cytokine secretion in a co-culture system. The HepG2, A549 and A375 cells displayed limited inhibitory effects. MCF-7 and MDA-MB-231 cells expressed the highest level of PD-L1 among the cells used, which may explain their higher immuno-suppressive effects. Compound A0-L, a small molecule inhibitor of the PD-1/PD-L1 interaction, restored T cell functions. Additionally, it was demonstrated that the tumor cells with higher levels of PD-L1 expression suppressed signaling pathways involved in T-cell activation, such as the T-cell receptor- zeta chain of T cell receptor associated protein kinase ZAP70-RAS-GTPase-extracellular-signal-regulated kinases and CD28-PI3K-Akt serine/threonine kinases pathways. These findings suggest that tumor cells with higher expression levels of PD-L1 may exhibit higher immuno-suppressive activity, and that drugs targeting the PD-1/PD-L1 interaction may have improved therapeutic effects on tumors expressing higher levels of PD-L1.

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Section: Introductionmentioning

confidence: 99%

PD‑L1 expression levels on tumor cells affect their immunosuppressive activity

Yang

Fang

2019

Oncol Lett

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“…Immune checkpoints are immune system negative regulators that play crucial roles in maintaining self-tolerance, avoiding autoimmunity, and protecting tissues from immune collateral harm. [29] In cancer, immune checkpoints had a critical role in the tumor-related immune Table 2 In GC samples, the correlations between the immune cell marker genes and NT5DC2 expression.…”

Section: Discussionmentioning

confidence: 99%

Gastric cancer metastasis-related NT5DC2 indicates unfavorable prognosis of patients

Sha,

Zhang,

Meng

et al. 2023

Medicine

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Purpose: Approximately 80 to 90% of patients with gastric cancer (GC) eventually develop into metastatic GC nowadays,because GC is difficult to be diagnosed at an early stage. GC patients with metastases typically have a poor prognosis. It is necessary to explore a potential prognostic marker in metastatic GC. Methods: All GC data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The metastasis-related candidate gene and its role in GC were analyzed by comprehensive analysis. Results: Totally 1049 metastasis-related genes were identified in GC. Univariate Cox regression analysis screened the top 10 genes (PDHX, SLC43A1, CSAG2, NT5DC2, CSAG1, FMN1, MED1, HIVEP2, FNDC3A, and PPP1R2) that were closely correlated with prognosis of GC patients. Among which, NT5DC2 was screened as the target gene for subsequent study. The NT5DC2 expression were increased in primary GC and metastatic GC samples. Moreover, GC patients with high NT5DC2 expression exhibited shorter overall survival and post progression survival, and the NT5DC2 was metastatic GC patients’ independent prognostic factor. Totally 29 pathways were activated in metastatic GC samples with high NT5DC2 expression. Four immune cells’ infiltration were significantly different between NT5DC2 high and low expressed metastatic GC patients. NT5DC2 showed significantly negative correlations with 6 types of immune cells’ critical marker genes and 5 types of immune cell infiltration. The 10 immune checkpoint expressions were decreased in high NTDC2 expression metastatic GC patients. Conclusions: NT5DC2 plays a prognostic role in metastatic GC. GC patients with high NT5DC2 expression indicates unfavorable prognosis.

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“…Immune checkpoints were negative regulators in immune system. They participated in the prevented autoimmunity and protected tissues from immune damage 47 . It has been demonstrated that inhibition of immune checkpoints could enhance the anti-tumor immunity in cancers 48 , 49 .…”

Section: Discussionmentioning

confidence: 99%

HER2 low expression breast cancer subtyping and their correlation with prognosis and immune landscape based on the histone modification related genes

Li,

Yao,

2023

Sci Rep

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Human epidermal growth factor receptor 2 (HER2) plays an important role in diagnosis and treatment of breast cancer (BRCA). The histone modification has been found to be related to the progression of cancer. This study aimed to probe the low HER2 expression BRCA heterogeneity by histone modification genes. The BRCA data and cell lines were collected from The Cancer Genome Atlas database. Weighted gene co-expression network analysis and non-negative matrix factorization clustering were jointly applied to obtain BRCA clusters. The expression of hub histone modification gene was detected using western blot assay. The gene ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to reveal functional information. The overall survival analysis was performed using survival and survminer packages, and the immune landscape was mainly analyzed using CIBERSORT software. Totally 43 histone modification genes correlated with survival of BRCA patients with HER2 low expression were screened. Based on these 43 histone modification genes, the BRCA samples were classified into cluster1, cluster2 and cluster3. Histone modification gene NFKBIZ exhibited high expression, while RAD51 demonstrated low expression in low HER2 expression BRCA cell. Cluster1 exhibited the best prognosis, while cluster3 had the worse outcomes. Tumor mutational burden (TMB) was remarkably increased in cluster3 group compared to cluster1 and cluster2. Moreover, the relative proportion of 16 immune cell infiltration and 8 immune checkpoint expression were remarkably differential among cluster1, cluster2 and cluster3, and the drug sensitivity exhibited difference among cluster1, cluster2 and cluster3 in BRCA patients with low HER2 expression. This study identified three HER2 low expression BRCA clusters with different characteristics based on histone modification genes. The TMB, immune cell infiltration, immune checkpoints and drug sensitivity were different among the three clusters.

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Dynamics of Immune Checkpoints, Immune System, and BCG in the Treatment of Superficial Bladder Cancer

Cited by 13 publications

References 28 publications

PD‑L1 expression levels on tumor cells affect their immunosuppressive activity

PD‑L1 expression levels on tumor cells affect their immunosuppressive activity

Gastric cancer metastasis-related NT5DC2 indicates unfavorable prognosis of patients

HER2 low expression breast cancer subtyping and their correlation with prognosis and immune landscape based on the histone modification related genes

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