Characterisation of immune checkpoints in Richter syndrome identifies LAG3 as a potential therapeutic target
- Author(s)
- Gould, C; Lickiss, J; Kankanige, Y; Yerneni, S; Lade, S; Gandhi, MK; Chin, C; Yannakou, CK; Villa, D; Slack, GW; Markham, JF; Tam, CS; Nelson, N; Seymour, JF; Dickinson, M; Neeson, PJ; Westerman, D; Blombery, P;
- Journal Title
- British Journal of Haematology
- Publication Type
- epub ahead of print
- Abstract
- Richter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B-cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS. Formalin-fixed, paraffin-embedded biopsies of RS (n = 19), de novo diffuse large B-cell lymphoma (DLBCL; n = 58), transformed indolent lymphomas (follicular [tFL], n = 16; marginal zone [tMZL], n = 24) and non-transformed small lymphocytic lymphoma (SLL; n = 15) underwent gene expression profiling using the NanoString Human Immunology panel. Copy number assessment was performed using next-generation sequencing. Immunohistochemistry (IHC) for LAG3 and PD-1 was performed. LAG3 gene expression was higher in RS compared to DLBCL (P = 0·0002, log2FC 1·96), tFL (P < 0·0001, log2FC 2·61), tMZL (P = 0·0004, log2FC 1·79) and SLL (P = 0·0057, log2FC 1·45). LAG3 gene expression correlated with the gene expression of human leukocyte antigen Class I and II, and related immune genes and immune checkpoints. IHC revealed LAG3 protein expression on both malignant RS cells and tumour-infiltrating lymphocytes. Our findings support the investigation of LAG3 inhibition to enhance anti-tumour responses in RS.
- Publisher
- Wiley
- Research Division(s)
- Bioinformatics
- PubMed ID
- 34426978
- Publisher's Version
- https://doi.org/10.1111/bjh.17789
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-09-17 11:04:07
Last Modified: 2021-09-17 11:08:16