Tertiary lymphoid structures (TLS) correlate with favorable responses to cancer immunotherapy, yet the mechanisms driving their formation and maintenance remain unclear. Using spatial mapping across human tumors, we found consistent accumulation of CCR7⁺ mature dendritic cells (DCs) within TLS. To study their role, we developed a NSCLC model forming mature TLS. TLS induction required IFNγ-driven cDC1 maturation, migration to tumor-draining lymph nodes (TdLNs), and recruitment of TdLN-primed T cells. As tumors progressed, TLS persisted without TdLN egress, coinciding with impaired cDC1 migration and their retention in CCR7 ligand-enriched intratumoral stromal hubs. Timed cDC1 depletion or impeded localization to these hubs disrupted TLS maintenance. Loss of MHC-I and II on cDC1 abrogated the maintenance of TLS, TFH cells, germinal centers, tumor-specific IgG production, and differentiation of progenitor exhausted CD8⁺ T cells. These findings show that local cDC1-mediated activation of CD8⁺ and CD4⁺ T cells sustains TLS and represents a therapeutic opportunity.
About the speaker
Raphaël Mattiuz is an AACR postdoctoral fellow in Dr. Miriam Merad’s lab at the Icahn School of Medicine at Mount Sinai (New York), where he investigates how dendritic cells (DCs) orchestrate the formation and maintenance of tertiary lymphoid structures (TLS) in cancer.
He completed his PhD at the Centre d’Immunologie de Marseille-Luminy (CIML) in the laboratory of Dr. Marc Dalod, focusing on cDC1-mediated control of T cell responses in breast cancer immunosurveillance. Prior to that, he trained in mucosal immunology and epigenetics at Institut Cochin (Paris) and the Babraham Institute (Cambridge, UK).
He has also contributed to recent studies on the role of aging and IL-4 signaling in myelopoiesis and macrophage dysfunction in lung cancer. His future research aims to dissect how myeloid cells regulate TLS functionality and local immune memory across cancer, infection, and chronic inflammatory diseases.
