Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan;16(1):41-56.
doi: 10.2217/epi-2023-0358. Epub 2024 Jan 15.

Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer

Ji-Qing Chen  1 , Lucas A Salas  1 , John K Wiencke  2 , Devin C Koestler  3 , Annette M Molinaro  2 , Angeline S Andrew  4 , John D Seigne  5 , Margaret R Karagas  1 , Karl T Kelsey  6 , Brock C Christensen  1   7
Affiliations

Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer

Ji-Qing Chen et al. Epigenomics. 2024 Jan.

Abstract

Background: Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are limited. Methods: DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering. Results: Immune hot and cold groups had different immune compositions in the TME but not in circulating blood. Two clusters of patients identified with consensus clustering had different immune compositions not only in the TME but also in blood. Conclusion: Detailed immune profiling via methylation cytometry reveals the significance of understanding tumor and systemic immune relationships in cancer patients.

Keywords: DNA methylation; bladder cancer; circulating immune profiles; immune profiles; methylation cytometry; tumor microenvironment.

Plain language summary

Bladder cancer and treatment outcomes depend on the immune profiles in the tumor and blood. Our study, using DNA methylation cytometry, measured immune cell proportions in both areas. Patients were grouped based on immune status and consensus clustering. Results showed distinct immune compositions in the tumor, but not in blood, for hot and cold groups. Consensus clustering revealed two patient clusters with differing immune compositions in both tumor and blood. This detailed immune profiling highlights the importance of understanding the complex interplay between tumor and systemic immunity in bladder cancer patients.

PubMed Disclaimer

Conflict of interest statement

Competing interests disclosure

J Wiencke and K Kelsey are co-founders of Cellintec, which had no role in this work. B Christensen is an advisor to Guardant Health which had no role in this work. The funders had no role in study design, data collection, data analysis, or data interpretation. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, stock ownership or options, and expert testimony.

Figures

Figure 1.
Figure 1.. Data processing and cell distribution in tumor microenvironment and peripheral blood.
(A) Data processing schematic. DNA was extracted from tumor tissues and matched blood samples of 88 bladder cancer patients. After serial preprocessing steps, DNA methylation profiles were applied to estimate cell-type proportions in (B) tumor tissues and (C) blood using HiTIMED and FlowSorted.Blood.EPIC methods respectively. NLR: Neutrophil-to-lymphocyte ratio.
Figure 2.
Figure 2.. Cell profiles of tumor microenvironment in non-muscle-invasive and muscle-invasive bladder cancer patients.
Differences in cell-type proportions between NMIBC and MIBC patients were evaluated using the Wilcoxon rank sum test. MIBC: Muscle-invasive bladder cancer; NMIBC: Non-muscle-invasive bladder cancer.
Figure 3.
Figure 3.. Tumor and blood cell profiles distribution of two groups assigned by the proportion of antitumor immune infiltration.
The high immune infiltration group (High) consisted of the 50 patients who had the sum of B, CD8 T, CD4 T, natural killer and dendritic cell proportions >5% in the tumor microenvironment. The low immune infiltration group (Low) consisted of the 38 patients who had the sum of B, CD8 T, CD4 T, natural killer and dendritic cell proportions ≤5% in the tumor microenvironment. Differences in cell-type proportions between two groups were evaluated using the Wilcoxon rank sum test.
Figure 4.
Figure 4.. Tumor and blood cell profiles distribution of two groups assigned by consensus clustering algorithm using tumor immune profiles as input.
Group 1 and group 2 consisted of 43 and 45 patients, respectively. Differences in cell-type proportions between two groups were evaluated using the Wilcoxon rank sum test.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Liu Y-N, Zhang H, Zhang L et al. Sphingosine 1 phosphate receptor-1 (S1P1) promotes tumor-associated regulatory T cell expansion: leading to poor survival in bladder cancer. Cell Death Dis. 10(2), 50 (2019). - PMC - PubMed
    1. Loskog A, Ninalga C, Paul-Wetterberg G, de la Torre M, Malmström P-U, Tötterman TH. Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines. J. Urol. 177(1), 353–358 (2007). - PubMed
    1. Zhang H, Ye Y-L, Li M-X et al. CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer. Oncogene 36(15), 2095–2104 (2017). - PubMed
    1. Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19(2), 108–119 (2018). - PMC - PubMed
    1. Wu K, Tan M-Y, Jiang J-T et al. Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: a novel chemoimmunomodulating strategy. Clin. Immunol. 193, 60–69 (2018). - PubMed