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Distinct Infiltration of T Cell Populations in Bladder Cancer Molecular Subtypes

Sincic, Viktor LU ; Arlenhold, Ken F. ; Richtmann, Sarah LU ; Lilljebjörn, Henrik LU orcid ; Eriksson, Pontus LU ; Sjödahl, Gottfrid LU ; Wokander, Mats ; Hägerbrand, Karin LU ; Ellmark, Peter LU and Fioretos, Thoas LU , et al. (2024) In Cells 13(11).
Abstract

Bladder cancer is a heterogenous disease, and molecular subtyping is a promising method to capture this variability. Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal/Squamous (Ba/Sq) and genomically unstable (GU)... (More)

Bladder cancer is a heterogenous disease, and molecular subtyping is a promising method to capture this variability. Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal/Squamous (Ba/Sq) and genomically unstable (GU) tumors displayed increased immune infiltration compared to urothelial-like (Uro) tumors. Additionally, the GU tumors had a higher proportion of regulatory T cells within the immune compartment compared to Uro tumors. Furthermore, sequencing showed higher levels of exhaustion in CD8+ T cells from GU tumors compared to both Uro tumors and the control. Although no such difference was detected at the transcriptomic level in Uro tumors compared to the controls, CD8+ T cells in Uro tumors showed higher expression of several exhaustion markers at the protein level. Taken together, our findings indicate that depending on the molecular subtype, different immunotherapeutic interventions might be warranted.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bladder cancer, exhaustion, immunotherapy, molecular subtypes, T cell population
in
Cells
volume
13
issue
11
article number
926
publisher
MDPI AG
external identifiers
  • scopus:85195832095
ISSN
2073-4409
DOI
10.3390/cells13110926
language
English
LU publication?
yes
id
e699b349-8753-4f5a-b113-4da371457df5
date added to LUP
2024-08-20 12:56:12
date last changed
2024-08-20 12:57:37
@article{e699b349-8753-4f5a-b113-4da371457df5,
  abstract     = {{<p>Bladder cancer is a heterogenous disease, and molecular subtyping is a promising method to capture this variability. Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal/Squamous (Ba/Sq) and genomically unstable (GU) tumors displayed increased immune infiltration compared to urothelial-like (Uro) tumors. Additionally, the GU tumors had a higher proportion of regulatory T cells within the immune compartment compared to Uro tumors. Furthermore, sequencing showed higher levels of exhaustion in CD8<sup>+</sup> T cells from GU tumors compared to both Uro tumors and the control. Although no such difference was detected at the transcriptomic level in Uro tumors compared to the controls, CD8<sup>+</sup> T cells in Uro tumors showed higher expression of several exhaustion markers at the protein level. Taken together, our findings indicate that depending on the molecular subtype, different immunotherapeutic interventions might be warranted.</p>}},
  author       = {{Sincic, Viktor and Arlenhold, Ken F. and Richtmann, Sarah and Lilljebjörn, Henrik and Eriksson, Pontus and Sjödahl, Gottfrid and Wokander, Mats and Hägerbrand, Karin and Ellmark, Peter and Fioretos, Thoas and Borrebaeck, Carl A.K. and Liedberg, Fredrik and Lundberg, Kristina}},
  issn         = {{2073-4409}},
  keywords     = {{bladder cancer; exhaustion; immunotherapy; molecular subtypes; T cell population}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Distinct Infiltration of T Cell Populations in Bladder Cancer Molecular Subtypes}},
  url          = {{http://dx.doi.org/10.3390/cells13110926}},
  doi          = {{10.3390/cells13110926}},
  volume       = {{13}},
  year         = {{2024}},
}