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Antigen-presenting B cells promote TCF-1 + PD1 - stem-like CD8 + T-cell proliferation in glioblastoma.
- Source :
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Frontiers in immunology [Front Immunol] 2024 Jan 10; Vol. 14, pp. 1295218. Date of Electronic Publication: 2024 Jan 10 (Print Publication: 2023). - Publication Year :
- 2024
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Abstract
- Understanding the spatial relationship and functional interaction of immune cells in glioblastoma (GBM) is critical for developing new therapeutics that overcome the highly immunosuppressive tumor microenvironment. Our study showed that B and T cells form clusters within the GBM microenvironment within a 15-μm radius, suggesting that B and T cells could form immune synapses within the GBM. However, GBM-infiltrating B cells suppress the activation of CD8 <superscript>+</superscript> T cells. To overcome this immunosuppression, we leveraged B-cell functions by activating them with CD40 agonism, IFNγ, and BAFF to generate a potent antigen-presenting B cells named B <subscript>Vax</subscript> . B <subscript>Vax</subscript> had improved antigen cross-presentation potential compared to naïve B cells and were primed to use the IL15-IL15Ra mechanism to enhance T cell activation. Compared to naïve B cells, B <subscript>Vax</subscript> could improve CD8 T cell activation and proliferation. Compared to dendritic cells (DCs), which are the current gold standard professional antigen-presenting cell, B <subscript>Vax</subscript> promoted highly proliferative T cells in-vitro that had a stem-like memory T cell phenotype characterized by CD62L <superscript>+</superscript> CD44 <superscript>-</superscript> expression, high TCF-1 expression, and low PD-1 and granzyme B expression. Adoptive transfer of B <subscript>Vax</subscript> -activated CD8 <superscript>+</superscript> T cells into tumor-bearing brains led to T cell reactivation with higher TCF-1 expression and elevated granzyme B production compared to DC-activated CD8 <superscript>+</superscript> T cells. Adoptive transfer of B <subscript>Vax</subscript> into an irradiated immunocompetent tumor-bearing host promoted more CD8 <superscript>+</superscript> T cell proliferation than adoptive transfer of DCs. Moreover, highly proliferative CD8 <superscript>+</superscript> T cells in the B <subscript>Vax</subscript> group had less PD-1 expression than those highly proliferative CD8 <superscript>+</superscript> T cells in the DC group. The findings of this study suggest that B <subscript>Vax</subscript> and DC could generate distinctive CD8 <superscript>+</superscript> T cells, which potentially serve multiple purposes in cellular vaccine development.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Hou, Wan, Katz, Wang, Castro, Vazquez-Cervantes, Arrieta, Dhiantravan, Najem, Rashidi, Chia, Arjmandi, Collado, Billingham, Lopez-Rosas, Han, Sonabend, Heimberger, Zhang, Miska and Lee-Chang.)
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38268923
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1295218