Yangyang Qi1, Yuan Chang2, Zewei Wang3, Lingli Chen4, Yunyi Kong5, Peipei Zhang6, Zheng Liu2, Quan Zhou7, Yifan Chen1, Jiajun Wang3, Qi Bai3, Yu Xia3, Li Liu3, Yu Zhu2, Le Xu8, Bo Dai2, Jianming Guo3, Yiwei Wang9, Jiejie Xu10, Weijuan Zhang11. 1. Department of Immunology, School of Basic Medical Sciences, Fudan University, Building West 13, No. 138 Yixueyuan Road, Shanghai, 200032, China. 2. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China. 3. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. 4. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China. 5. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. 6. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 7. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Building West 7, No. 138 Yixueyuan Road, Shanghai, 200032, China. 8. Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 9. Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Manufacturing Bureau Road, Shanghai, 200011, China. wang.yiwei@sh9hospital.org. 10. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Building West 7, No. 138 Yixueyuan Road, Shanghai, 200032, China. jjxufdu@fudan.edu.cn. 11. Department of Immunology, School of Basic Medical Sciences, Fudan University, Building West 13, No. 138 Yixueyuan Road, Shanghai, 200032, China. weijuanzhang@fudan.edu.cn.
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.
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 MIBCpatients. High Gal-9+TAMs were associated with a pro-tumor immune contexture concomitant with T cell exhaustion.
Authors: Nan Xiao; Kangshuai Li; Xiaodong Zhu; Bin Xu; Xuefeng Liu; Ming Lei; Hui-Chuan Sun Journal: Cancer Immunol Immunother Date: 2021-05-19 Impact factor: 6.968
Authors: Michal Hensler; Lenka Kasikova; Karel Fiser; Jana Rakova; Petr Skapa; Jan Laco; Tereza Lanickova; Ladislav Pecen; Iva Truxova; Sarka Vosahlikova; Irena Moserova; Ivan Praznovec; Vit Drochytek; Martina Rehackova; Tomas Brtnicky; Lukas Rob; Vladimir Benes; Jelena Pistolic; Ludek Sojka; Ales Ryska; Catherine Sautes-Fridman; Wolf Herve Fridman; Lorenzo Galluzzi; Radek Spisek; Jitka Fucikova Journal: J Immunother Cancer Date: 2020-08 Impact factor: 13.751