Dendritic Cell–T Cell Crosstalk as a Central Driver of Response and Resistance to Immune Checkpoint Therapies
<p>Dendritic cells (DCs) are emerging as central orchestrators of antitumor immunity, shaping the quality, magnitude, and persistence of T-cell responses within the tumor microenvironment. Growing evidence shows that successful immune checkpoint therapies (ICT) depend on highly coordinated DC–...
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| Autores principales: | , |
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| Formato: | Capítulo de libro |
| Lenguaje: | inglés |
| Publicado: |
IntechOpen
2026
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| Materias: | |
| Acceso en línea: | https://www.intechopen.com/chapters/1242895 |
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| Sumario: | <p>Dendritic cells (DCs) are emerging as central orchestrators of antitumor immunity, shaping the quality, magnitude, and persistence of T-cell responses within the tumor microenvironment. Growing evidence shows that successful immune checkpoint therapies (ICT) depend on highly coordinated DC–T cell crosstalk, rather than on ICT acting on T cells alone. Although ICT restores cytotoxic function by targeting immune checkpoint regulators, such as CTLA-4 and PD-1, they primarily amplify preexisting immune responses established during earlier stages of immune priming. These upstream events are critically governed by DCs, which capture tumor antigens, process and cross-present them to CD8⁺ T cells, and instruct CD4⁺ helper differentiation across lymphoid tissues and tumors. Tumor-driven disruption of DC differentiation, migration, antigen presentation, and costimulatory signaling creates immunological bottlenecks that limit T-cell priming and contribute to therapeutic resistance. Specialized subsets, such as cDC1, play a dominant role in cross-presentation, yet tumor-derived signals frequently reprogram DCs into dysfunctional or checkpoint-constrained states. Beyond antigen display, reciprocal cytokine circuits, spatial immune niches, and inhibitory ligand expression at the DC–T cell interface critically determine responsiveness to ICT. In this chapter, we examine how DC programming, antigen presentation dynamics, and DC–T cell crosstalk shape immune recognition, resistance, and clinical response to ICT. We further discuss emerging myeloid-intrinsic checkpoint regulators and therapeutic strategies aimed at restoring DC immunogenicity. We conclude that durable ICT responses require not only T-cell reinvigoration but also rational reactivation of DC function as a foundational layer of antitumor immunity and new rational combinatorial approaches.</p> |
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| ISBN: | 978-1-80631-619-9 |
| DOI: | 10.5772/intechopen.1015805 |