Eric Vivier "Innate lymphoid cells: from discovery to therapy"

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Séminaire Eric Vivier

Centre d’Immunologie de Marseille-Luminy, Aix Marseille Univ, CNRS, INSERM, 13288 Marseille, France Service d’Immunologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France

 

 

"Innate lymphoid cells: from discovery to therapy"

 

Résumé

Less than ten years after their initial description, the comprehension of innate lymphoid cells (ILCs) biology is rapidly improving. ILCs can be classified on the basis of their similarity to T cell subsets in terms of their cytokine production and expression of key transcription factors. Various immunological functions of ILCs have been described, and increasing numbers of studies have implicated these cells in immune responses. Using models of selective ILC depletion and studying cohorts of patients with severe ILC deficiency, we could show that ILCs appear redundant for protective immunity in conditions of modern hygiene and medicine, if T and B cell functions are preserved. However, ILCs appear to be critical for the onset or the maintenance of several inflammatory disorders such as asthma, chronic rhinosinusitis, atopic dermatitis, inflammatory bowel diseases, psoriasis, systemic or organ-specific inflammatory and autoimmune diseases. Future directions in the field will be discussed, together with potential avenues of treatment.

Recent research advances have also shed new light on the role the immune system plays in advanced-stage cancer. Immunotherapies have terribly increased in numbers and in diversity. Among immune effectors suitable for manipulation, Natural Killer (NK) cells are of particular interest. They are a population of ILCs that can induce the death of allogeneic and autologous cells undergoing malignant transformation and microbial infection. Early studies showing the importance of NK cells in the anti-tumor response were performed in mice. Several studies have shown a link in humans between low NK cell activity in peripheral blood and an increased risk of cancer. In addition, tumor infiltration by NK cells has been shown to be a favorable prognostic factor in non-small cell lung cancer (NSCLC), clear cell renal cell cancer and colorectal cancer. Immune Checkpoint Inhibitors (ICI) have been shown to be effective and to have manageable safety profiles for several cancer types. Their use has resulted in long-term survival, for more than a decade, in some patients with cancers for which significant therapeutic advances have been made, such as metastatic melanoma and NSCLC. Along these lines, a therapeutic mAb blocking the three inhibitory KIR receptors for HLA-C was generated: Lirilumab (IPH2102, BMS-986015). Lirilumab is a fully human recombinant IgG4 that increases NK cell cytotoxicity against HLA-C-expressing tumor cells. The results of the effect of Lirilumab in clincal trials will be reviewed.

Invitation : Cécile Contin-Bordes – ImmunoConcept CNRS UMR 5164

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  • Nom : Rocher Virginie