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Updated: Aug 6, 2026
09:51
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Dendritic cells control tertiary lymphoid structure development and maintenance in cancer
Raphaël Mattiuz1,2, Jesse Boumelha1,2, Emmanouil Aerakis1,2,3
1Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Science (New York, N.Y.)
|July 16, 2026
Summary
Tertiary lymphoid structures (TLSs) are crucial for immunotherapy response. Mature dendritic cells (DCs) orchestrate TLS formation and function within tumors, offering new therapeutic targets to boost anticancer immunity.
Area of Science:
- Immunology
- Cancer Biology
- Tumor Microenvironment
Background:
- Tertiary lymphoid structures (TLSs) are increasingly recognized for their role in predicting and mediating responses to cancer immunotherapy.
- However, the precise cellular and molecular mechanisms governing TLS formation, maturation, and maintenance within the tumor microenvironment remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanisms controlling the formation and maintenance of tertiary lymphoid structures (TLSs) in tumors.
- To identify the key cellular players and signaling pathways involved in TLS orchestration.
- To explore the potential of targeting these mechanisms for enhancing antitumor immunity.
Main Methods:
- Spatial transcriptomics and multiplex imaging were employed on human tumor samples.
- A mouse model of non-small cell lung cancer (NSCLC) with mature TLS formation was utilized.
- Analysis included dendritic cell (DC) maturation, migration, antigen presentation, and T cell recruitment dynamics.
Main Results:
- Mature CCR7+ dendritic cells (DCs) were found to accumulate within TLSs across human tumors.
- Early TLS development in a mouse NSCLC model depended on interferon-γ (IFN-γ)-driven type 1 conventional dendritic cell (cDC1) maturation and migration.
- Persistent TLSs in progressing tumors were linked to intratumoral cDC1 accumulation in CCL19+ stromal hubs, where they sustained TLS, T follicular helper (TFH) cells, germinal centers, and IgG production via MHC-I/II antigen presentation and CD40 signaling.
Conclusions:
- Local mature cDC1s are identified as critical orchestrators of TLS formation and function within the tumor microenvironment.
- These cDC1s play a pivotal role in sustaining the adaptive immune response within TLSs, independent of lymph node T cell egress.
- Targeting intratumoral cDC1s and their associated signaling pathways presents a promising strategy for enhancing TLS-mediated antitumor immunity and immunotherapy efficacy.
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