Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

Labadie, Brian; Balar, Arjun Vasant; Luke, Jason J.

doi:10.3390/cancers13215415

Cited by 22 publications

(13 citation statements)

References 221 publications

(283 reference statements)

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“…In immune checkpoint analysis, CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, etc., while SIGLEC15 was highly expressed in cluster 1. No consensus has been reached on the predictive value of immune checkpoints in BC immunotherapy, such as PD-L1 and CTLA4 [ 33 ]. In theory, an immunosuppressive microenvironment promotes the expression of immune checkpoints, as presented in the present study.…”

Section: Discussionmentioning

confidence: 99%

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

Feng

Wang

et al. 2023

Eur J Med Res

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Background N7-methylguanosine (m7G) is closely associated with tumor prognosis and immune response in many cancer types. The correlation between m7G and bladder cancer (BC) needs further study. We aimed to orchestrate molecular subtypes and identify key genes for BC from the perspective of m7G. Methods RNA-seq and clinical data of BC patients were extracted from TCGA and GSE13507 datasets. The patients were subtyped by “ConsensusClusterPlus” and “limma.” The clusters were validated by the Kaplan‒Meier curves, univariable and multivariate Cox regression models, the concordance index, and calibration curves. The immunotherapy response was evaluated by immune checkpoints, immune infiltration, TIDE score, and IMvigor210 cohort. Genomics of Drug Sensitivity in Cancer was utilized to predict the chemotherapy response between the clusters. Results The m7G-related cluster was ultimately established by EIF4G1, NUDT11, NUDT10, and CCNB1. The independent prognostic value of the m7G-related cluster was validated by the TCGA and GSE13507 datasets. The cluster was involved in immune-associated pathways, such as neutrophil degranulation, antigen processing cross-presentation, and signaling by interleukins pathways. Meanwhile, cluster 2 was positively correlated with many immune checkpoints, such as CD274, CTLA4, HAVCR2, LAG3, PDCD1, and PDCD1LG2. The cluster 2 was significantly correlated with a higher TIDE score than the cluster 1. Furthermore, in the IMvigor210 cohort, patients in the cluster 1 had a higher response rate than those in the cluster 2. Patients in the cluster 2 were sensitive to many chemotherapies. Conclusions We successfully determined molecular subtypes and identified key genes for BC from the perspective of m7G, thereby providing a roadmap for the evolution of immunotherapy and precision medicine.

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Section: Discussionmentioning

confidence: 99%

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

Feng

Wang

et al. 2023

Eur J Med Res

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“…Currently, the insidious onset of RCC and the lack of specific clinical signs in the early stages result in 20-30% of patients having metastases by the time of presentation (22). As KIRC has been studied more intensively, immunotherapy has been found to significantly improve the prognosis of patients (23)(24)(25). Results of completed clinical trials have shown various other immunomodulatory pathways in the tumor immune microenvironment, which can affect tumor cell survival and significantly influence immunotherapeutic response (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma

Pei

Wang

et al. 2022

Front. Oncol.

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BackgroundThe tumor microenvironment (TME) is a complex and evolving environment, and the tumor immune microenvironment in kidney renal clear cell carcinoma (KIRC) has a strong suppressive profile. This study investigates the potential prognostic role and value of genes of the tumor microenvironment in KIRC.MethodsThe transcriptome sequencing data of 530 cases and 39 cases of KIRC and the corresponding clinical prognosis information were downloaded from TCGA data and GEO data, respectively, and TME-related gene expression profiles were extracted. A prognostic signature was constructed and evaluated using univariate Cox regression analysis and LASSO regression analysis. Gene set enrichment analysis (GSEA) was used to obtain the biological process of gene enrichment in patients with high and low-risk groups.ResultsA prognostic signature consisting of eight TME-related genes (LRFN1, CSF1, UCN, TUBB2B, SERPINF1, ADAM8, ABCB4, CCL22) was constructed. Kaplan-Meier survival analysis yielded significantly lower survival times for patients in the high-risk group than in the low-risk group, and the AUC values for the ROC curves of this prognostic signature were essentially greater than 0.7, and univariate and multifactorial Cox regression analyses indicated that the risk score was independent risk factors for KIRC prognosis. GSEA analysis showed that immune-related biological processes were enriched in the high-risk group and that risk values were strongly associated with multiple immune cell scores and immune checkpoint-related genes (PDCD1, CTLA4).ConclusionsThe prognostic signature can accurately predict the prognosis of KIRC patients, which may provide new ideas for future precision immunotherapy of KIRC.

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“…It is well known that immunotherapy, and particularly immune checkpoint inhibitors (ICIs) targeting the T-cell receptor–ligand interaction, such as cytotoxic lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death ligand 1 (PD-L1) [ 20 ], have made major advances in the last decade and are widely used in clinical practice to treat urological tumors [ 21 ], such as renal cell carcinoma [ 22 ] and urothelial cancer [ 23 ]. However, in mPC the results have to date been quite modest, except for a small subgroup of mCRPC patients (3–5%) that present a microsatellite instability (MSI) and mismatch repair-deficient (dMMR) phenotype in which exceptional responses to the anti-PD-1 pembrolizumab have been reported [ 24 , 25 , 26 ].…”

Section: Immunotherapy In Metastatic Prostate Cancer Treatment: Current Status and Mechanisms Of Resistancementioning

confidence: 99%

Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?

Martori

Sanchez‐Moral

Paul

et al. 2022

Cancers

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Prostate cancer (PC) is the most common malignancy and the fifth cause of cancer death in men. The treatment for localized or locally advanced stages offers a high probability of cure. Even though the therapeutic landscape has significantly improved over the last decade, metastatic PC (mPC) still has a poor prognosis mainly due to the development of therapy resistance. In this context, the use of immunotherapy alone or in combination with other drugs has been explored in recent years. However, T-cell directed immune checkpoint inhibitors (ICIs) have shown limited activity with inconclusive results in mPC patients, most likely due to the highly immunosuppressive PC tumor microenvironment (TME). In this scenario, targeting macrophages, a highly abundant immunosuppressive cell type in the TME, could offer a new therapeutic strategy to improve immunotherapy efficacy. In this review, we summarize the growing field of macrophage-directed immunotherapies and discuss how these could be applied in the treatment of mPC, focusing on their combination with ICIs.

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Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

Cited by 22 publications

References 221 publications

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma

Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?

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