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Poor clinical outcomes and immunoevasive contexture in SIRPα+ tumor-associated macrophages enriched muscle-invasive bladder cancer patients.
- Source :
-
Urologic Oncology . Mar2022, Vol. 40 Issue 3, p109.e11-109.e20. 1p. - Publication Year :
- 2022
-
Abstract
- <bold>Objectives: </bold>In tumor immune microenvironment, the functions of tumor-associated macrophages (TAMs), including phagocytosis and immunomodulatory, have attracted increasing attention recently. With the discovery of CD47-signal regulatory protein-α (SIRPα) as "don't eat me" signaling pathway, the role of novel subpopulation of TAMs expressing SIRPα has not been fully elucidated in a wide spectrum of solid tumors including bladder cancer. In this study, we investigated the prognostic and predictive implication of SIRPα+ TAMs regarding clinical outcomes and adjuvant chemotherapeutic benefit in muscle-invasive bladder cancer (MIBC), and preliminarily characterized the phenotypic features of SIRPα+ TAMs and its relationship with immune contexture.<bold>Materials and Methods: </bold>A total of 141 histochemical MIBC samples from Zhongshan Hospital (ZS), 45 fresh tissue samples, and 391 MIBC patients from TCGA database were enrolled in this study. SIRPα+ TAMs was evaluated by immunohistochemical staining of CD68 and SIRPα, and flow cytometry fluorescence staining.<bold>Results: </bold>Our results illustrated that SIRPα+ TAMs were enriched in MIBC specimens. Patients with high SIRPα+ TAMs infiltration suffered significant poor overall survival and recurrence-free survival (P = 0.0030 and P = 0.0282). SIRPα+ TAMs infiltration was an independent prognosticator in multivariate Cox model. Moreover, adjuvant chemotherapy (ACT) application showed significantly survival benefit in patients with low SIRPα+ TAMs infiltration (P = 0.0135). SIRPα+ TAMs with suppressive phenotype exhibited a positive correlation with immune tolerance and dysfunctional CD8+ T cells in MIBC.<bold>Conclusions: </bold>SIRPα+ TAMs infiltration indicated poor prognosis and ACT resistance in MIBC. Immunosuppressive SIRPα+ TAMs is closely related to immune evasion with exhausted T cells states, suggesting the prospect of SIRPα+ TAMs as a potential therapeutic target in MIBC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10781439
- Volume :
- 40
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Urologic Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 155400305
- Full Text :
- https://doi.org/10.1016/j.urolonc.2021.08.024