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Sex differences in the aging murine urinary bladder and influence on the tumor immune microenvironment of a carcinogen-induced model of bladder cancer.
Hamade, Ali; Li, Deyang; Tyryshkin, Kathrin; Xu, Minqi; Conseil, Gwenaelle; Yolmo, Priyanka; Hamilton, Jake; Chenard, Stephen; Robert Siemens, D; Koti, Madhuri.
Afiliação
  • Hamade A; Queen's Cancer Research Institute, Kingston, ON, Canada.
  • Li D; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Tyryshkin K; Queen's Cancer Research Institute, Kingston, ON, Canada.
  • Xu M; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Conseil G; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
  • Yolmo P; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
  • Hamilton J; Queen's Cancer Research Institute, Kingston, ON, Canada.
  • Chenard S; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Robert Siemens D; Queen's Cancer Research Institute, Kingston, ON, Canada.
  • Koti M; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Biol Sex Differ ; 13(1): 19, 2022 05 03.
Article em En | MEDLINE | ID: mdl-35505436
Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sex differences in the tumor immune microenvironment of non-muscle invasive and muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches to more precisely recapitulate these differences towards improved therapeutic design. Given the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence-based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell mediated responses. Spatial profiling of healthy bladders, using markers specific to macrophages, T cells, B cells, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice also showed a higher presence of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age associated differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of bladder cancer and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Carcinoma de Células de Transição Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Biol Sex Differ Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Canadá País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Carcinoma de Células de Transição Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Biol Sex Differ Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Canadá País de publicação: Reino Unido