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El Halabi, Layal; Adam, Julien; Gravelle, Pauline; Marty, Virginie; Danu, Alina; Lazarovici, Julien; Ribrag, Vincent; Bosq, Jacques; Camara-Clayette, Valérie; Laurent, Camille; Ghez, David
Clinical lymphoma, myeloma and leukemia, April 2021, 2021-04-00, 20210401, Volume: 21, Issue: 4Journal Article
The role of the programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis is well established in classical Hodgkin lymphoma (HL), where PD-1 blockade demonstrated spectacular efficacy in relapsed/refractory disease. However, little is known about the frequency and cellular distribution of other immune checkpoints in HL samples. Using immunohistochemistry, we investigated, along with PD-L1 and PD-1, the expression of lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) in 57 biopsy samples of patients with classical HL. Hodgkin and Reed/Sternberg (HRS) cells were strongly positive for PD-L1 in nearly all cases. HRS cells were TIM-3 positive in 36% of samples, whereas LAG-3 was rarely expressed (5.2%). In the microenvironment, PD-1, LAG-3, and TIM-3 were expressed by ≥ 5% of cells in 65%, 98%, and 96% of cases, respectively. T-cell rosettes surrounding HRS cells consisted of CD4+ FoxP3− helper T cells expressing both PD-1 and LAG-3, with a variable expression of TIM-3. This study demonstrates for the first time that LAG-3 and TIM-3 are nearly always expressed in the microenvironment of classical HL. This may constitute the basis for targeting LAG-3 or TIM-3 in combination with anti–PD-1 antibodies in the treatment of relapsed/refractory HL. •Lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) are nearly always expressed in the tumor microenvironment of classical Hodgkin lymphoma.•TIM-3 is expressed by Hodgkin and Reed/Sternberg cells in a third of the cases. Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking agents are used in relapsed/refractory classical Hodgkin lymphoma (HL), while other immune checkpoints such as lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) may also play a role. By performing immunohistochemistry on 57 biopsy samples, we found that TIM-3 was expressed by Hodgkin and Reed/Sternberg cells in 36% of the cases, and LAG-3 and TIM-3 were widely expressed in the tumor microenvironment. LAG-3 and TIM-3 may constitute therapeutic targets in the treatment of HL.
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