TY - JOUR T1 - Immunosuppressive tumor-associated macrophages expressing interlukin-10 conferred poor prognosis and therapeutic vulnerability in patients with muscle-invasive bladder cancer JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2021-003416 VL - 10 IS - 3 SP - e003416 AU - Yijia Xu AU - Han Zeng AU - Kaifeng Jin AU - Zhaopei Liu AU - Yu Zhu AU - Le Xu AU - Zewei Wang AU - Yuan Chang AU - Jiejie Xu Y1 - 2022/03/01 UR - http://jitc.bmj.com/content/10/3/e003416.abstract N2 - Background Tumor-associated macrophages (TAMs) secreting IL-10 could be a specific functional cell subset with distinct polarization state and suppressive role in antitumor immune response. Here, we assessed the associations of clinical outcome, therapeutic responses and molecular features with IL-10+TAMs infiltration, and potential impact of IL-10+TAMs on the immune contexture in muscle-invasive bladder cancer (MIBC).Methods In this retrospective study, 128 patients and 391 patients with MIBC from Zhongshan hospital (ZS cohort) and The Cancer Genome Atlas cohort were included respectively. Immunohistochemistry was performed to quantify various immune cell infiltration in the ZS cohort. Single cell RNA sequencing and flow cytometry were performed to examine the functional status of IL-10+TAMs and its correlation with other immune cells. Survival analyses and assessment of the adjuvant chemotherapy (ACT) benefit analyses were also performed.Results High IL-10+TAMs infiltration was associated with inferior prognosis in terms of overall survival and recurrence-free survival, but superior chemotherapeutic response in MIBC. IL-10+TAMs with suppressive features were associated with immunoevasive tumor microenviroment characterized by exhausted CD8+ T cells, immature NK cells and increased immune checkpoint expression. Additionally, high IL-10+TAMs infiltration showed a strong linkage with basal-featured subtype and augmented EGF signaling.Conclusions Immunosuppresive IL-10+TAMs contributed to an evasive contexture with incapacitated immune effector cells and increased immune checkpoint expression, therefore, predicting unfavorable clinical outcomes despite better ACT responsiveness. IL-10+TAMs might provide guidance for customized selection of EGFR-targeted therapy, FGFR3-targeted therapy as well as immunotherapy. The potential of immunosuppressive IL-10+TAMs as a therapeutic target is worth further exploration.Data are available on reasonable request. All data generated that are relevant to the results presented in this article are included in this article. Other data that were not relevant for the results presented here are available from the corresponding author JX on reasonable request. ER -