Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort

The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried o...

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Published in:International journal of molecular sciences 2017-10, Vol.18 (10), p.2186
Main Authors: Miyake, Makito, Tatsumi, Yoshihiro, Gotoh, Daisuke, Ohnishi, Sayuri, Owari, Takuya, Iida, Kota, Ohnishi, Kenta, Hori, Shunta, Morizawa, Yosuke, Itami, Yoshitaka, Nakai, Yasushi, Inoue, Takeshi, Anai, Satoshi, Torimoto, Kazumasa, Aoki, Katsuya, Shimada, Keiji, Konishi, Noboru, Tanaka, Nobumichi, Fujimoto, Kiyohide
Format: Article
Language:English
Subjects:
Bacillus Calmette-Guerin vaccine
BCG
Bladder cancer
Cancer
Forkhead protein
Foxp3 protein
Immunoregulation
Interleukin 6
Invasiveness
Lymphocytes
Lymphocytes T
Macrophages
Patients
Urinary bladder
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Summary:The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried out immunohistochemical analysis of forkhead box P3 (FOXP3, Treg maker), CD204 (TAM marker), and interleukin-6 (IL6) using surgical specimens obtained from 154 NMIBC patients. The Treg and TAM counts surrounding the cancer lesion and IL6-positive cancer cell counts were evaluated against clinicopathological variables. We focused on the ability of the Treg and TAM counts around the cancer lesion to predict outcomes after adjuvant intravesical Bacille Calmette-Guérin (BCG) treatment. High Treg counts were associated with female patients, older age, T1 category, and high tumor grade. TAM count was significantly correlated with Treg count and with IL6-positive cancer cell count. In our analysis of 71 patients treated with BCG, high counts of Treg and TAM were associated with shorter recurrence-free survival, and the former was an independent predictor of recurrence. Poor response to intravesical BCG was associated with Treg and TAM in the tumor microenvironment. Disrupting the immune network can be a supplementary therapeutic approach for NMIBC patients receiving intravesical BCG.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms18102186