Conventional type-1 DC density is associated with checkpoint inhibitor response across multiple types of cancer
Year: 2026
Type: article
Abstract: Conventional type-1 dendritic cells (cDC1) are the main mediators of crosspresentation of tumor antigens to CD8+ T cells and provide a context of costimulatory molecules and cytokines that lead to cytotoxic T lymphocyte (CTL) responses. We analyzed bulk RNA sequences from 7 key clinical trials testing checkpoint inhibitors across multiple cancer types. cDC1- and CD8-associated gene signatures were analyzed. Multiplex tissue immunofluorescence was used to quantify cDC1 in melanoma, urothelial cancer, and non-small-cell lung cancer (NSCLC) samples and assess cDC1 tissue neighborhoods. Melanoma samples were studied with Xenium spatial transcriptomics (ST) and one series of NSCLC was analyzed using GeoMX-DSP. Strong associations across tumor types were found between cDC1 and CD8+ T cell transcripts with clinical outcomes. As mechanistically expected, transcripts for the CCL4 and CCL5 chemokines and the growth factor FLT3-L showed associations with cDC1 abundance. Tissue immunofluorescence showed a strong correlation of cDC1 and CD8+ T cell infiltration with clinical benefit upon treatment with checkpoint inhibitors (CPIs). Moreover, short distance between cDC1 and CD8+ T cells was found to define tissue niches associated with favorable outcomes. ST revealed recent T cell activation within immune cDC1-rich niches. cDC1 abundance, which determines CD8+ T lymphocyte density and activation in tumor tissues across cancer types, is strongly associated with clinical response to CPI-based immunotherapies.
DOI: 10.1172/jci200987
Authors: Alvaro Lopez-Janeiro, José González-Gomariz, Fadi Issa, Joanna Hester, Angelo Porciuncula, Alvaro Teijeira, Carlos Luri-Rey, David Ruiz-Guillamon, Jose Luis Perez-Gracia, Elisabeth Perez-Ruiz, Isabel Barragan, Salvador Martín-Algarra, Miguel F. Sanmamed, Ignacio Ortego, Maria E. Rodriguez-Ruiz, Raluca Alexandru, Inmaculada Rodriguez, Saioa Arrieta-Aranzueque, David Rimm, Thazin Aung, Kurt A. Schalper, Carlos E. de Andrea, Ignacio Melero
Institutions: Clinica Universidad de Navarra, Universidad de Navarra, Centro de Investigación Médica Aplicada, University of Oxford, Yale University, Navarre Institute of Health Research, Centro de Investigación Biomédica en Red de Cáncer, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga, Karolinska Institutet, Hospital Clínico Universitario Virgen de la Victoria
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
OpenAlex ID: W7159685286