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CANCER IMMUNOTHERAPY

MR1-restricted pan-cancer T cells

Nature Reviews Immunology volume 20, page 141 (2020)Cite this article

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Current T cell-based cancer therapies are personalized to each patient (to ensure HLA matching) and are only suitable against certain cancers (with known target antigens). So the idea of a T cell-based therapy that is not limited by polymorphic MHC restriction or known tumour antigens is very attractive. A study published in Nature Immunology describes a new T cell population that specifically kills many human cancer cell types via recognition of the non-polymorphic MHC class I-related protein MR1. MR1 is widely expressed and varies little between individuals, raising the prospect of a universal cancer immunotherapy.

MR1 molecules presenting intermediates of riboflavin synthesis are known to be sensed by mucosal-associated invariant T (MAIT) cells. But MC.7.G5 T cells did not recognize MR1 bound with MAIT cell-activating ligands nor empty MR1 molecules or MR1 expressed by healthy monocyte-derived dendritic cells. Moreover, target cell recognition by MC.7.G5 T cells was reduced in the presence of riboflavin-derived microbial MR1 ligands. This suggested that MC.7.G5 T cells recognize MR1 molecules presenting cargo that is specific to cancer cells. Importantly with respect to their potential use as cancer immunotherapy, MC.7.G5 T cells remained unresponsive to healthy cells from various tissues even after MR1 surface expression was upregulated by cell activation or after exposure to cell stressors.

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References

Original article

  • Crowther, M. D. et al. Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nat. Immunol. 21, 178–185 (2020)

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Lucy Bird

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  1. Lucy Bird
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Correspondence to Lucy Bird.

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Bird, L. MR1-restricted pan-cancer T cells. Nat Rev Immunol 20, 141 (2020). https://doi.org/10.1038/s41577-020-0284-7

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