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Cancer Immunol Res. 2019 Jan 18. pii: canimm.0351.2018. doi: 10.1158/2326-6066.CIR-18-0351. [Epub ahead of print]

TIGIT and PD-1 mark intratumoral T cells with reduced effector function in B-cell non-Hodgkin lymphoma.

Author information

1
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital.
2
Department of Pathology, Oslo University Hospital Radiumhospitalet and Institute of Clinical Medicine, Medical Faculty, University of Oslo.
3
Institute for Cancer Research, Department of Cancer Immunology, Oslo University Hospital.
4
Department of Pathology, Oslo University Hospital.
5
Department of Oncology, Oslo University Hospital.
6
Division of Cancer Medicine, Surgery and Transplantation, Department of Oncology, Oslo University Hospital.
7
Dept. of Medicine, Div. of Hematology, HematologyCenter, Karolinska University Hospital, Stockholm, Sweden.
8
Section for Cellular Therapy, Department for Cancer Treatment, Oslo University Hospital.
9
Department of Cellular Therapy, Oslo University Hospital Radiumhospitalet.
10
Department of Cancer Immunology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
11
Department of Immunology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital.
12
Division of Oncology, Stanford University Hospital and Clinics.
13
Department of Oncology, Division of Cancer Medicine, Oslo University Hospital.
14
1Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital June.Helen.Myklebust@rr-research.no.

Abstract

Checkpoint blockade can reverse T-cell exhaustion and promote antitumor responses. Although blocking the PD-1 pathway has been successful in Hodgkin lymphoma, response rates have been modest in B-cell non-Hodgkin lymphoma (NHL). Co-blockade of checkpoint receptors may therefore be necessary to optimize antitumor T-cell responses. Here, characterization of co-inhibitory receptor expression in intratumoral T cells from different NHL types identified TIGIT and PD-1 as frequently expressed co-inhibitory receptors. Tumors from NHL patients were enriched in CD8+ and CD4+ TEM cells that displayed high co-expression of TIGIT and PD-1, and co-expression of these checkpoint receptors identified T cells with reduced production of IFN-γ, TNF-α and IL-2. The suppressed cytokine production could be improved upon in vitro culture in absence of ligands. Whereas PD-L1 was expressed by macrophages, the TIGIT ligands CD155 and CD112 were expressed by lymphoma cells in 39% and 50% of DLBCL cases and in some MCL cases, as well as by endothelium and FDCs in all NHLs investigated. Collectively, our results show that TIGIT and PD-1 mark dysfunctional T cells and suggest that TIGIT and PD-1 co-blockade should be further explored to elicit potent antitumor responses in patients with NHL.

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