Tumor-associated macrophages and Tregs influence and represent immune cell infiltration of muscle-invasive bladder cancer and predict prognosis

Autor: Florestan J. Koll, Severine Banek, Luis Kluth, Jens Köllermann, Katrin Bankov, Felix K.-H. Chun, Peter J. Wild, Andreas Weigert, Henning Reis
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-12 (2023)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-023-03949-3
Popis: Abstract Introduction and objective Muscle-invasive urothelial bladder cancer (MIBC) is associated with limited response rates to systemic therapy, risk of recurrence and death. Tumor infiltrating immune cells have been associated with outcome and response to chemo-and immunotherapy in MIBC. We aimed to profile the immune cells in the tumor microenvironment (TME) to predict prognosis in MIBC and responses to adjuvant chemotherapy. Methods We performed multiplex immunohistochemistry (IHC) profiling and quantification of immune and stromal cells (CD3, CD4, CD8, CD163, FoxP3, PD-1, and CD45, Vimentin, αSMA, PD-L1, Pan-Cytokeratin, Ki67) in 101 patients with MIBC receiving radical cystectomy. We used uni- and multivariate survival analyses to identify cell types predicting prognosis. Samples were subdivided using K-means clustering for Treg and macrophage infiltration resulting in 3 clusters, Cluster 1: Treg high, cluster 2: macrophage high, cluster 3: Treg and macrophage low. Routine CD68 and CD163 IHC were analyzed with QuPath in an extended cohort of 141 MIBC. Results High concentrations of macrophages were associated with increased risk of death (HR 10.9, 95% CI 2.8–40.5; p
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