by Kaykobad Hossain
Bladder cancer, like most cancers, is a heterogenous disease and the variability of the disease can be captured using molecular subtyping, which may result in more effective treatment options. Even though bladder cancer has been classified to multiple subtypes, the composition of immune compartment for each subtype is poorly understood.
In this study, the researchers investigated the immune infiltrations and immune compartment compositions for non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) cancers along with different molecular subtypes (Basal Ba /Squamous Sq, genomically unstable and urothelial-like tumors) of bladder cancer samples from patients. They assessed CD45+ immune cells infiltration and the relative abundance of helper T cells (Th), Tregs and cytotoxic CD8+ T cells using flow cytometry and RNA sequencing. In addition, transcriptomic differences of CD8+ T cells in genomically unstable (GU) and urothelial-like (Uro) tumors were also investigated.
The results showed that higher immune infiltration was associated with the invasiveness of the disease. However, the heterogeneity of tumor immune microenvironment was poorly understood. Even though higher immune infiltration was observed for the samples with MIBC, there was no significant difference in immune cell composition (proportion of CD3+, CD8+, CD4+, Th or Treg out of all CD45+ cells) between NMIBC and MIBC. However, the different molecular subtypes of BC showed to possess distinct immune microenvironments. When compared to Uro subtype, the immune infiltration was considerably higher in the Ba/Sq and GU subtypes, and similar T cell infiltration (CD3+ cells out of viable cells) was also observed. Of note, the proportions of CD4+ T cells and CD4/CD8 ratio within the immune compartment were higher in the Uro and GU subtypes compared to the Bs/Sq subtype. In addition, the immune compartment of GU subtype had enriched levels of Tregs, but not Th cells, compared to Uro group. Finally, the exhaustion profile of CD8+ T cells from GU group had more enriched exhaustion genes compared to Uro subtype and controls, and the differentially expressed genes by CD8+ T cells from GU and Uro tumors were mostly related to cell cycle and immune signaling.
These findings indicate that the molecular subtypes of bladder cancer possess characteristic immune microenvironments and understanding these environments may facilitate identification of better immunotherapy options against bladder cancer.
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Sincic V, Arlenhold KF, Richtmann S, Lilljebjörn H, Eriksson P, Sjödahl G, Wokander M, Hägerbrand K, Ellmark P, Fioretos T, Borrebaeck CAK, Liedberg F, Lundberg K. Distinct Infiltration of T Cell Populations in Bladder Cancer Molecular Subtypes. Cells 2024, 13(11), 926; https://doi.org/10.3390/cells13110926