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12.11.2019 | Original Article

Tumor-associated macrophages expressing galectin-9 identify immunoevasive subtype muscle-invasive bladder cancer with poor prognosis but favorable adjuvant chemotherapeutic response

verfasst von: Yangyang Qi, Yuan Chang, Zewei Wang, Lingli Chen, Yunyi Kong, Peipei Zhang, Zheng Liu, Quan Zhou, Yifan Chen, Jiajun Wang, Qi Bai, Yu Xia, Li Liu, Yu Zhu, Le Xu, Bo Dai, Jianming Guo, Yiwei Wang, Jiejie Xu, Weijuan Zhang

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 12/2019

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Abstract

Purpose

Tumor-associated macrophages (TAMs) exist as heterogeneous subsets and have dichotomous roles in cancer-immune evasion. This study aims to assess the clinical effects of Galectin-9⁺ tumor-associated macrophages (Gal-9⁺TAMs) in muscle-invasive bladder cancer (MIBC).

Experimental design

We identified Gal-9⁺TAMs by immunohistochemistry (IHC) analysis of a tumor microarray (TMA) (n = 141) from the Zhongshan Hospital and by flow cytometric analysis of tumor specimens (n = 20) from the Shanghai Cancer Center. The survival benefit of platinum-based chemotherapy in this subpopulation was evaluated. The effect of the tumor-immune microenvironment with different percentages of Gal-9⁺TAMs was explored.

Results

The frequency of Gal-9⁺TAMs increased with tumor stage and grade. Gal-9⁺TAMs predicted poor overall survival (OS) and recurrence-free survival (RFS) and were better than Gal-9⁻TAMs and TAMs to discriminate prognostic groups. In univariate and multivariate Cox regression analyses, patients with high percentages of Gal-9⁺TAMs showed the prominent survival benefit after receiving adjuvant chemotherapy (ACT). High Gal-9⁺TAM infiltration correlated with increasing numbers of regulatory T cells (Tregs) and mast cells and decreasing numbers of CD8⁺T and dendritic cells (DCs). Dense infiltration of Gal-9⁺TAMs was related to reduced cytotoxic molecules, enhanced immune checkpoints or immunosuppressive cytokines expressed by immune cells, as well as active proliferation of tumor cells. Additionally, the subpopulation accumulated was strongly associated with PD-1⁺TIM-3⁺CD8⁺T cells.

Conclusions

Gal-9⁺TAMs predicted OS and RFS and response to ACT in MIBC patients. High Gal-9⁺TAMs were associated with a pro-tumor immune contexture concomitant with T cell exhaustion.

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Titel: Tumor-associated macrophages expressing galectin-9 identify immunoevasive subtype muscle-invasive bladder cancer with poor prognosis but favorable adjuvant chemotherapeutic response
verfasst von: Yangyang Qi
Yuan Chang
Zewei Wang
Lingli Chen
Yunyi Kong
Peipei Zhang
Zheng Liu
Quan Zhou
Yifan Chen
Jiajun Wang
Qi Bai
Yu Xia
Li Liu
Yu Zhu
Le Xu
Bo Dai
Jianming Guo
Yiwei Wang
Jiejie Xu
Weijuan Zhang
Publikationsdatum: 12.11.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 12/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02429-2

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Tumor-associated macrophages expressing galectin-9 identify immunoevasive subtype muscle-invasive bladder cancer with poor prognosis but favorable adjuvant chemotherapeutic response