Marie Caroline Dieu-Nosjean
M-C. Dieu-Nosjean has first studied the biology and migratory capacity of human dendritic cells. Her work has gained insights to several inflammatory diseases including skin pathologies. More recently, she studied the immune microenvironment of lung tumors, and contributed to the characterization of tertiary lymphoid structures in cancer patients. During her career, she has authored more than 50 peer-reviewed reports and 4 patents. Dr. M-C. Dieu-Nosjean is Associate-Editor for Frontiers in Immunology. She is a member of the French Society of Immunology.
It is well established that a high level of infiltration of memory T cells withTh1 or cytotoxic orientation correlates with long-term survival in most human cancers. However, a key question remains: where does the activation of tumor-specific T cells take place? We recently described, tumor-associated lymph node-like entities termed “tertiary lymphoid structures” (TLS) in primary and metastatic lung cancers. TLS exhibit a structural organization that is reminiscent of secondary lymphoid organs. Lung tumor-associated TLS present a specific chemo-attractant signature associated with T cell infiltration. High endothelial venules selectively co-localize with TLS suggesting that TLS provide a key hub for the recruitment of peripheral blood immune cells into the tumor. We demonstrated that TLS are critical for the local coordination and polarization of protective immunity.Moreover, the presence of mature DC is required to license the positive prognostic value of tumor-infiltrating CD8+ T cells suggesting that TLS may imprint the behavior of intra-tumoralCD8+ T cells. NSCLC-associated TLS are also composed of a B-cell follicle where somatic hypermutation and class switch recombination machineries are activated.We showed that the density of follicular B cells is associated with a favorable clinical outcome, and correlates with the density of plasma cells. These data strongly suggest that TLS play a protective role against tumors by promoting an humoral immune response in lung cancer patients. In conclusion, TLS presenceis accompanied by profoundlocal modifications and systemic effects, as TLShave an impact on the tumor micro-architecture, immune microenvironment, and ultimately, cancer patient survival.