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Oncoimmunology. 2018 Dec 17;8(3):1554175. doi: 10.1080/2162402X.2018.1554175. eCollection 2019.

Boosting γδ T cell-mediated antibody-dependent cellular cytotoxicity by PD-1 blockade in follicular lymphoma.

Rossi C1,2,3,4,5, Gravelle P1,2,3,4,6, Decaup E1, Bordenave J1,2,3,4, Poupot M1,2,3,4, Tosolini M1,2,3,7, Franchini DM1,2,3,4, Laurent C1,2,3,4,6, Morin R8, Lagarde JM8, Ysebaert L1,2,3,4,9, Ligat L1,7, Jean C1, Savina A10, Klein C11, Céspedes AM12, Perez-Galan P12, Fournié JJ1,2,3,4, Bezombes C1,2,3,4.

Author information

1
Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 INSERM, Université Toulouse III: Paul-Sabatier, ERL5294 CNRS, Université de Toulouse, Toulouse, France.
2
Laboratoire d'Excellence TOUCAN, Toulouse, France.
3
Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France.
4
CALYM Carnot Institute, Pierre-Bénite, France.
5
CHU Dijon, Hématologie clinique, Hôpital François Mitterand, Dijon, France.
6
Department of Pathology, Institut Universitaire du Cancer de Toulouse, Toulouse, France.
7
Pôle Technologique du Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.
8
Imactiv 3D, Toulouse, France.
9
Department of Hematology, Institut Universitaire du Cancer de Toulouse, Toulouse, France.
10
Institut Roche, Boulogne Billancourt, France.
11
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich, Schlieren, Switzerland.
12
Hematology-Oncology department, IDIBAPS, Center Esther Koplowitz, Barcelona, Spain.

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.

KEYWORDS:

3D model; PD-1; anti-CD20 MAbs; follicular lymphoma; γδ T cells

PMID:
30723586
PMCID:
PMC6350687
[Available on 2019-12-17]
DOI:
10.1080/2162402X.2018.1554175

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