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Related Experiment Videos

Basal-subtype bladder tumours show a 'hot' immunophenotype.

Anjelica Hodgson1,2, Stanley K Liu3, Danny Vesprini3

  • 1Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Histopathology
|June 28, 2018
PubMed
Summary
This summary is machine-generated.

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Basal-subtype high-grade urothelial carcinoma (UC) exhibits a "hot" immune microenvironment with abundant CD8+ T cells and increased inhibitory markers. This immunophenotype is associated with specific immune cell profiles and a trend towards worse survival in muscle-invasive UC.

Area of Science:

  • Oncology
  • Immunology
  • Urothelial Carcinoma Research

Background:

  • Muscle-invasive urothelial carcinoma (UC) has distinct molecular subtypes (basal and luminal) impacting treatment response and outcomes.
  • High-grade UC elicits a significant immune response, with immune cell phenotypes potentially offering prognostic and predictive value.
  • Understanding the immune microenvironment's composition is crucial for developing targeted therapies.

Purpose of the Study:

  • To correlate the immunohistochemical phenotype of high-grade UC with its immune microenvironment composition.
  • To investigate differences in immune cell infiltration and marker expression between basal and luminal UC subtypes.
  • To explore the prognostic implications of these immune characteristics.

Main Methods:

Keywords:
PD-L1immune cell typingimmune microenvironmentimmunophenotypeurothelial carcinoma

Related Experiment Videos

  • Review of 235 high-grade UC cases treated with cystectomy, recording clinicopathological variables and survival data.
  • Construction of tissue microarrays (TMAs) stained for cytokeratin (CK) 5/6 and GATA3 to classify tumors into basal or luminal subtypes.
  • Sequential TMA staining for immune markers (CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, PD-1, PD-L1) to analyze immune cell composition.

    • Main Results:

    • 167 luminal (CK5/6-, GATA3+) and 29 basal (CK5/6+, GATA3-) subtypes were identified.
    • Basal-subtype tumors showed a trend towards worse disease-specific survival (P=0.078).
    • Significant associations were found between basal subtype and increased CD8, PD-1, and PD-L1 expression (P<0.05).
    • Basal subtype also displayed lower CD4/CD8 and higher CD8/FOXP3 ratios (P<0.05).

    Conclusions:

    • Basal-subtype high-grade UC is characterized by an abundance of CD8+ T cells.
    • This subtype exhibits increased expression of inhibitory markers like PD-1 and PD-L1.
    • These findings indicate a 'hot' immunophenotype in basal UC, suggesting potential for immunotherapy.