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Patients with refractory relapsed multiple myeloma (RRMM) respond to Elotuzumab (Elo) and lenalidomide (Len) combination treatment. The mechanisms underlying this observation are not fully understood. Furthermore, predictive biomarkers of response have not been revealed to date. To address these issues, we used a humanized myeloma mouse model and adoptive transfer of human NK cells to show that Elo and Len treatment controlled myeloma growth, and this was mediated through CD16 on NK cells. In co-culture studies, we showed that PBMCs from a subset of RRMM patients were effective killers of OPM2 myeloma cells when treated with Elo and Len, and this was associated with significantly increased expression of CD54 expression on OPM2 cells. Furthermore, Elo and Len induced OPM2 cell killing and increased OPM2 CD54 expression was dependent on both monocytes and NK cells, and was not mediated by soluble factors alone. At the transcript level, Elo and Len treatment significantly increased OPM2 myeloma cell expression of genes for trafficking and adhesion molecules, NK cell activation ligands and antigen presentation molecules. In conclusion, our findings suggest that MM patients require Elo and Len-mediated upregulation of CD54 on the autologous myeloma cells, in combination with NK cells and monocytes to mediate an effective anti-tumour response. Further, our data suggest that increased myeloma cell CD54 expression levels could be a powerful predictive biomarker for response to Elo and Len treatment.

MR1-restricted mucosal-associated invariant T (MAIT) cells recognize microbial metabolites and play an important role in immunity to infection, however, the role they play in tumor immunity is unclear. Here we show that MAIT cell-deficient mice are more resistant to subcutaneous and lung metastasis B16F10 tumor growth compared to control mice, an effect that was associated with enhanced NK cell numbers and was NK cell-dependent. Analysis of this interplay in cancer patients also revealed that a high expression of a novel MAIT gene signature negatively impacted the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or antigen-mediated MAIT cell activation in vivo, enhanced immunity against B16F10 and E0771 lung tumor metastasis. Furthermore, MAIT cell activation effectively reduced metastatic burden in a more stringent model of established lung metastases in mice. These effects were associated with enhanced NK cell responses and increased expression of both IFNγ-dependent and inflammatory genes in NK cells, which was neutralized by IFNγ blockade. Importantly, activated human MAIT cells also enhanced the function of NK cells isolated from patient tumor samples. These findings provide insight into the contrasting roles that MAIT cells can play in controlling anti-tumor immune responses depending on their activation status, in both mice and humans, and suggest potential therapeutic avenues for exploiting their potential anti-tumor properties for cancer treatment.

A new species, Alexandrium camurascutulum sp. nov. MacKenzie et Todd, is described from specimens collected from Tasman Bay and the Marlborough Sounds New Zealand. These small (26–28 μm long × 21–24 μm wide) cells can be discriminated from other species in the Alexandrium minutum group by three distinctive morphological features. The sixth pre-cingular plate (6′′) is up to 1.6 times wider than high and the left side of the plate is concave resulting in a markedly ‘hooked’ appearance. In all specimens observed, the first apical plate (1′) does not directly connect with the apical pore plate (Po) and the posterior sulcal plate (S.p.) is markedly different from the usual A. minutum form and may contain a posterior attachment pore (pap) connected to the right side plate margin. The cells may or may not have an anterior attachment pore (aap) in the apical pore plate (Po). The cells display a prominent list along the left sulcal margin and the thecal surface is perforated with numerous areolated pores. A. camurascutulum sp. nov. has been observed occasionally over a number of years in coastal waters of the northern South Island of New Zealand. There is circumstantial evidence that suggests it is not toxic.