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Progression of AITL-like tumors in mice is driven by Tfh signature proteins and T-B cross talk.
Witalis, Mariko; Chang, Jinsam; Zhong, Ming-Chao; Bouklouch, Yasser; Panneton, Vincent; Li, Joanna; Buch, Thorsten; Kim, Seok Jin; Kim, Won Seog; Ko, Young Hyeh; Veillette, André; Suh, Woong-Kyung.
Afiliación
  • Witalis M; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
  • Chang J; Molecular Biology Department, University of Montréal, Montréal, QC, Canada.
  • Zhong MC; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
  • Bouklouch Y; Molecular Biology Department, University of Montréal, Montréal, QC, Canada.
  • Panneton V; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
  • Li J; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
  • Buch T; Department of Experimental Medicine, McGill University, Montréal, QC, Canada.
  • Kim SJ; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
  • Kim WS; Department of Microbiology, Infectious Diseases, and Immunology, University of Montréal, Montréal, QC, Canada.
  • Ko YH; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC, Canada.
  • Veillette A; Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
  • Suh WK; Institute of Laboratory Animal Science, University of Zürich, Zürich, Switzerland; and.
Blood Adv ; 4(5): 868-879, 2020 03 10.
Article en En | MEDLINE | ID: mdl-32130407
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma driven by a pool of neoplastic cells originating from T follicular helper (Tfh) cells and concomitant expansion of B cells. Conventional chemotherapies for AITL have shown limited efficacy, and as such, there is a need for improved therapeutic options. Because AITL originates from Tfh cells, we hypothesized that AITL tumors continue to rely on essential Tfh components and intimate T-cell-B-cell (T-B) interactions. Using a spontaneous AITL mouse model (Roquinsan/+ mice), we found that acute loss of Bcl6 activity in growing tumors drastically reduced tumor size, demonstrating that AITL-like tumors critically depend on the Tfh lineage-defining transcription factor Bcl6. Because Bcl6 can upregulate expression of signaling lymphocytic activation molecule-associated protein (SAP), which is known to promote T-B conjugation, we next targeted the SAP-encoding Sh2d1a gene. We observed that Sh2d1a deletion from CD4+ T cells in fully developed tumors also led to tumor regression. Further, we provide evidence that tumor progression depends on T-B cross talk facilitated by SAP and high-affinity LFA-1. In our study, AITL-like tumors relied heavily on molecular pathways that support Tfh cell identity and T-B collaboration, revealing potential therapeutic targets for AITL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma de Células T Periférico / Linfadenopatía Inmunoblástica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Blood Adv Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma de Células T Periférico / Linfadenopatía Inmunoblástica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Blood Adv Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos