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Dendritic Cells and Immune Checkpoints Within the Tumor Microenvironment: Mechanisms, Models, and Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2100

Special Issue Editor


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Guest Editor
Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain
Interests: cancer; immunology; dendritic cells

Special Issue Information

Dear Colleagues,

Effective cancer immunotherapy depends not only on T-cell reinvigoration but also on the presence and functionality of dendritic cells (DCs) within the native tumor immune microenvironment. Checkpoint blockade and other immunostimulatory agents—such as agonists of STING, CD40, FLT3, or TLR pathways—ultimately rely on intratumoral DCs to capture antigens, mature appropriately, and prime or re-prime effector T-cells. Insufficient numbers or impaired activation of tumor-resident DC subsets have emerged as key barriers to response, while preserved DC niches correlate strongly with therapeutic benefit across cancers. Understanding these DC-dependent mechanisms requires experimental systems that maintain the full complexity of cancer immune infiltrates, including native myeloid, lymphoid, and stromal components.

This Special Issue welcomes studies dissecting how immune checkpoint inhibitors and immunostimulatory agents modulate DC biology, antigen presentation, and T-cell dynamics within tumor ecosystems. We encourage submissions leveraging advanced in situ and ex vivo approaches—such as spatial profiling, organoids retaining endogenous immune populations, and single-cell multi-omics—to reveal how DCs integrate microenvironmental cues and modulate sensitivity or resistance to immunotherapy. Work bridging mechanistic insights with translational or clinical findings is particularly valued.

Dr. Francisco J. Cueto
Guest Editor

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Keywords

  • tumor immune microenvironment
  • immune checkpoint blockade
  • dendritic cells
  • antigen presentation
  • T-cell responses

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Published Papers (1 paper)

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Research

28 pages, 5209 KB  
Article
Colorectal Air–Liquid Interface Organoids Preserve Tumour-Immune Architecture and Reveal Local Treg Expansion After PD-1 Blockade
by Laura Córdoba, Francisco J. Cueto, Ramón Cantero-Cid, Rebeca Abad-Moret, Esteban Díaz, Jaime Álvarez-Benayas, Jesús Fernández-Felipe, Jesús Jiménez-Rodríguez, Daniel Arvelo-Rosario, Pablo Mata-Martínez, Marina Arranz-Álvarez, Yaiza Pedroche-Just, Sandra Nieto-Torrero, Jaime Valentín-Quiroga, Verónica Terrón-Arcos, Jaime Fernández-Pascual, Paloma Gómez-Campelo, Nieves Cubo-Mateo, Olivia Fernández-Medina, Laura Hurtado-Navarro, Gonzalo Sáenz de Santa María, Julia del Prado-Montero, Agustín L. Santos, Roberto Lozano-Rodríguez, Carlos del Fresno and Eduardo López-Collazoadd Show full author list remove Hide full author list
Cancers 2026, 18(1), 132; https://doi.org/10.3390/cancers18010132 - 30 Dec 2025
Cited by 2 | Viewed by 1837
Abstract
Background/Objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air–liquid interface (ALI) organoid model [...] Read more.
Background/Objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air–liquid interface (ALI) organoid model to paired tumour and perilesional colon tissues from colorectal cancer patients to evaluate its ability to retain immune and genetic features and to reproduce responses to chemotherapy and immune checkpoint blockade. Methods: Fresh human tumour and matched healthy colon tissues were processed to generate ALI organoids. Their histological organization, immune cell composition (including CD45+ subsets), and genomic profiles were compared with those of the parental tissues and with conventional Matrigel organoids, either alone or co-cultured with peripheral blood mononuclear cells (PBMCs). Organoids were exposed to 5-FU and nivolumab (anti–PD-1) to assess local immune modulation. Results: ALI organoids faithfully preserved the three-dimensional architecture, native immune infiltrates, and somatic mutational landscape of the source tissues. Importantly, upon PD-1 blockade with nivolumab, ALI organoids consistently exhibited a local expansion of regulatory T cells (Tregs), a phenomenon that could contribute to adaptive immune resistance. This response was not reproduced in PBMC–Matrigel co-culture systems, highlighting the importance of preserving endogenous tumour–immune interactions. Conclusions: Patient-derived ALI organoids represent a physiologically relevant platform that conserves key structural, immunological, and genomic hallmarks of colorectal cancer. By capturing clinically relevant immune remodeling events, such as Treg expansion following PD-1 blockade, this model provides a powerful tool for dissecting tumour–immune interactions. Full article
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