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Infiltration and Polarization of Tumor-associated Macrophages Predict Prognosis and Therapeutic Benefit in Muscle-Invasive Bladder Cancer. | LitMetric

AI Article Synopsis

  • - Muscle-invasive bladder cancer (MIBC) is aggressive and characterized by tumor-associated macrophages (TAMs) that influence the tumor's inflammatory environment.
  • - A study involving 141 MIBC patients and data from 391 additional patients categorized TAMs into three subtypes, highlighting distinct prognoses and treatment benefits, especially noting that Subtype II responds better to adjuvant chemotherapy and PD-L1 blockade.
  • - The findings suggest that TAMs influence the immune landscape of MIBC, indicating the potential for tailored chemotherapy and immunotherapy based on the polarization and infiltration of these macrophages.

Article Abstract

Background: Muscle-invasive bladder cancer (MIBC) is an aggressive and heterogeneous malignancy. Tumor-associated macrophages (TAMs) are key infiltrating cell populations in the inflammatory microenvironment of malignant tumors including MIBC. It intrigues us to explore the clinical significance and immunoregulatory role of TAMs infiltration and polarization in MIBC.

Methods: A total of 141 patients with MIBC from Zhongshan Hospital and 391 patients with MIBC from The Cancer Genome Atlas (TCGA) database were included in this study. Moreover, 195 patients who received anti-PD-L1 therapy from the IMvigor210 trial were enrolled. Patients were categorized into three subtypes considering the infiltration level and polarization status of TAMs, denoted as TAM (Subtype I), TAM&M2/M1 (Subtype II), and TAM&M2/M1 (Subtype III).

Results: Subtype III suffered inferior prognosis, and Subtype II could benefit more from adjuvant chemotherapy (ACT). Subtype III was featured with increased pro-tumor cells and immunosuppressive cytokines, while Subtype II possessed more immunogenic cells infiltration with activated and tumoricidal properties. Subtype II and Subtype III presented basal/squamous-like characterization and showed additional prognostic merit beyond molecular classification. Subtype I exhibited elevated level of FGFR3 signature, while Subtype II had EGFR signaling activation and immunotherapeutic indication. Additionally, Subtype II patients were indeed highly sensitive to PD-L1 blockade therapy in IMvigor210 trial.

Conclusion: The infiltration and polarization status of TAMs shaped distinct immune microenvironment with predictive significance for survival outcome, ACT benefit, and PD-L1 blockade therapy sensitivity in MIBC. Immune classification based on TAMs polarization and infiltration might provide tools to tailor chemotherapy and immunotherapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10991313PMC
http://dx.doi.org/10.1007/s00262-021-03098-wDOI Listing

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