| Literature DB >> 30723586 |
Cédric Rossi1,2,3,4,5, Pauline Gravelle1,2,3,4,6, Emilie Decaup1, Julie Bordenave1,2,3,4, Mary Poupot1,2,3,4, Marie Tosolini1,2,3,7, Don-Marc Franchini1,2,3,4, Camille Laurent1,2,3,4,6, Renaud Morin8, Jean-Michel Lagarde8, Loïc Ysebaert1,2,3,4,9, Laetitia Ligat1,7, Christine Jean1, Ariel Savina10, Christian Klein11, Alba Matas Céspedes12, Patricia Perez-Galan12, Jean-Jacques Fournié1,2,3,4, Christine Bezombes1,2,3,4.
Abstract
Follicular lymphoma (FL) is a common non Hodgkin's lymphoma subtype in which immune escape mechanisms are implicated in resistance to chemo-immunotherapy. Although molecular studies point to qualitative and quantitative deregulation of immune checkpoints, in depth cellular analysis of FL immune escape is lacking. Here, by functional assays and in silico analyses we show that a subset of FL patients displays a 'high' immune escape phenotype. These FL cases are characterized by abundant infiltration of PD1+ CD16+ TCRVγ9Vδ2 γδ T lymphocytes. In a 3D co-culture assay (MALC), γδ T cells mediate both direct and indirect (ADCC in the presence of anti-CD20 mAbs) cytolytic activity against FL cell aggregates. Importantly, PD-1, which is expressed by most FL-infiltrating γδ T lymphocytes with ADCC capacity, impairs these functions. In conclusion, we identify a PD1-regulated γδ T cell cytolytic immune component in FL. Our data provide a treatment rational by PD-1 blockade aimed at boosting γδ T cell anti-tumor functions in FL.Entities:
Keywords: 3D model; PD-1; anti-CD20 MAbs; follicular lymphoma; γδ T cells
Year: 2018 PMID： 30723586 PMCID： PMC6350687 DOI： 10.1080/2162402X.2018.1554175
Source DB: PubMed Journal: Oncoimmunology ISSN： 2162-4011 Impact factor: 8.110