Dataset Information

Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer.

ABSTRACT:

Purpose

To explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

Methods

We prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and the expression of immunoregulatory molecules (Tim-3, TIGIT and PD-1). PBMC from healthy donors (HD) were included for comparison, and associations with response to BCG were investigated.

Results

A total of 38 patients were included, 19 BCG responders and 19 BCG refractory. Compared to 16 PBMC from HD, the frequency of total NK cells was significantly higher in patients with NMIBC [15.2% (IQR: 11.4, 22.2) vs. 5.72% (IQR: 4.84, 9.79); p = 0.05], whereas the frequency of T cells was not statistically different. Both Tim-3 and TIGIT expressions were significantly higher in NMIBC compared to HD, particularly in NK cells [13.8% (11.0; 22.4) vs. 5.56% (4.20; 10.2) and 34.9% (18.9; 53.5) vs. 1.82% (0.63; 5.16), respectively; p < 0.001]. Overall, the expression of PD-1 in all cell types was low in both NMIBC patients and HD. The immune phenotype was not significantly different before and after initiation of BCG. However, the proportion of CD8⁺ T cells before BCG was significantly higher in responders.

Conclusion

The immune phenotype of PBMC from patients with high-risk NMIBC was significantly different from HD, regardless of the presence of disease or the initiation of BCG. Peripheral CD8⁺ T cells could play a role in response to BCG.

SUBMITTER: Audenet F

PROVIDER: S-EPMC6207464 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer.

Audenet François F Farkas Adam M AM Anastos Harry H Galsky Matthew D MD Bhardwaj Nina N Sfakianos John P JP

World journal of urology 20180602 11

<h4>Purpose</h4>To explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC).<h4>Methods</h4>We prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and the expression of immunoregulatory molecules (Tim-3, TIGIT and PD-1). PBMC from healthy donors (HD) were included for compari ...[more]

PMID: 29860605

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Project description:BackgroundHigh-risk non-muscle-invasive bladder cancer (HR-NMIBC) presents a challenge to many physicians due to its ability to resist Bacillus Calmette-Guérin (BCG) intravesical therapy and the substantial rate of progression into muscle-invasive bladder cancer (MIBC). Patients who are BCG-unresponsive have worse prognosis and thus require further management including radical cystectomy (RC), which significantly impacts quality of life. Moreover, the ongoing worldwide shortage of BCG warrants the need for policies that prioritize drug use and utilize alternative treatment strategies. Hence, there is a significant unmet need for bladder preserving therapy in this subset of patients.MethodsTo address this issue, we searched the relevant literature in PUBMED for articles published from 2019 through May of 2023 using appropriate keywords. All clinical trials of patients with HR-NMIBC treated with immune-related agents were retrieved from clinicaltrials.gov.Findings and future perspectivesExploratory treatments for BCG-Unresponsive HR-NMIBC included immune checkpoint inhibitors (ICI), oncolytic viral therapy, cytokine agonists, and other immunomodulators targeting TLR, EpCaM, FGFR, MetAP2, and IDO1. Some combination therapies have been found to work synergistically and are preferred therapeutically over monotherapy. Three drugs-pembrolizumab, valrubicin, and most recently, nadofaragene firadenovec-vncg-have been FDA approved for the treatment of BCG-unresponsive NMIBC in patients who are ineligible for or decline RC. However, all explored treatment options tend to postpone RC rather than provide long-term disease control. Additional combination strategies need to be studied to enhance the effects of immunotherapy. Despite the challenges faced in finding effective therapies, many potential treatments are currently under investigation. Addressing the landscape of biomarkers, mechanisms of progression, BCG resistance, and trial design challenges in HR-NMIBC is essential for the discovery of new targets and the development of effective treatments.

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Dataset Information

Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer.

Purpose

Methods

Results

Conclusion

Publications

Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer.

Similar Datasets

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