Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presentedMultiple myeloma is a haematological malignancy characterised by a clonal outgrowth of malignant plasma cells in the bone marrow 1 . Advances in stem cell transplants and therapeutics over the last 15 years have seen major improvements in the long-term survival and quality of life of patients diagnosed with MM 2 , yet despite these advances, MM remains an incurable disease, with a median survival around 7 years 1 .The current treatment of MM is largely based on the doublet or triplet combinations of corticosteroids, proteasome inhibitors and/or immunomodulatory drugs (IMiDs) as induction therapy prior to autologous stem cell transplantation in younger patients. Lenalidomide (Len), is the most extensively used IMiD for the treatment of MM 3 . It has both direct anti-tumor and immune-mediated mechanisms of action through binding cereblon (CRBN), a component of an E3-ubiquitin ligase 4 . Len commonly forms the backbone of newly developed

The BCL6 Corepressor (BCOR) is a component of a variant Polycomb repressive complex 1 (PRC1) that is essential for normal development. Recurrent mutations in the BCOR gene have been identified in acute myeloid leukaemia and myelodysplastic syndrome among other cancers; however, its function remains poorly understood. Here we examine the role of BCOR in haematopoiesis in vivo using a conditional mouse model that mimics the mutations observed in haematological malignancies. Inactivation of Bcor in haematopoietic stem cells (HSCs) results in expansion of myeloid progenitors and co-operates with oncogenic KrasG12D in the initiation of an aggressive and fully transplantable acute leukaemia. Gene expression analysis and chromatin immunoprecipitation sequencing reveals differential regulation of a subset of PRC1-target genes including HSC-associated transcription factors such as Hoxa7/9. This study provides mechanistic understanding of how BCOR regulates cell fate decisions and how loss of function contributes to the development of leukaemia.

Key Points• The combination of elotuzumab and an anti-PD-1 antibody leads to enhanced antitumor efficacy in mouse models.• Enhanced antitumor activity is likely due to the promotion of tumorinfiltrating NK and T-cell activity. In these mouse models, elotuzumab-g2a and anti-PD-1 combination treatment promoted tumor-infiltrating NK and CD8 1 T-cell activation, as well as increased intratumoral cytokine and chemokine release. These observations support the rationale for clinical investigation of elotuzumab/anti-PD-1 combination therapy in patients with MM.

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