There is a new buzz within the cancer research community. The word on the grapevine is that breakthrough research just published may eventually lead to the long-awaited holy grail: a cure for all cancers! You may have read about this development in newspapers, seen it on the BBC or on social media, or you may even have seen videos about it on YouTube. It has everybody very excited…dare we imagine that the end to cancer is soon to be in sight?
What exactly has been found to cause such a stir? The pivotal study was published in Nature Immunology this month1, by a group based in Cardiff with collaborators from the USA, Denmark, and Australia. Necessarily, the publication is very technical, so here is a more digestible summary.
Cancer cells display molecules on their surface which are different to the molecules displayed on the surface of healthy cells. This is similar to virus-infected cells which present ‘red flag’ molecules on their surface which allows immune system T-cells to recognise them and destroy them. By using a genome-wide screening tool called CRISP-Cas9, the researchers were able to find a cancer cell surface molecule (‘ligand’) - held by a surface protein called MR1 - which is recognised by a T-cell clone. The result was that the T-cells killed the cancer cells, both in laboratory experiments and in a living animal model. Importantly, healthy cells were not harmed. What’s got people particularly excited is that this cancer recognition by a T-cell clone occurs in many cancer-cell types from a range of tissues. Clearly, this suggests that an effective treatment for many, if not all, cancers may be on the horizon.
But let’s not jump the gun. There is still a lot of work to do before the dream becomes a reality. The exact nature of the ligand recognized by the T-cell clone is still unknown – it may be a cancer-specific or cancer-associated metabolite. Results so far suggest that the ligand is part of a pathway essential for the survival of cancer cells. This work also needs to be demonstrated in human trials, which is no small task.
The foundations have been laid, so let’s be optimistic. Given that the T-cell clone can recognize diverse cancer cell types, including primary cancer cells, this research opens up exciting opportunities for pan-cancer, pan-population, T-cell-mediated cancer immunotherapy. Furthermore, discovery of other ligands recognized by similar T-cell clones may provide opportunities for therapeutic vaccination for many cancers in everybody.
There is much to be hopeful for. To paraphrase Winston Churchill, this is not yet the end for cancer; it may not even be the beginning of the end; but it might just be the end of the beginning in the search for a cure.
Crowther MD, Dolton G, Legut M, Caillaud ME, Lloyd A, Attaf M, et al. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nat Immunol 2020 Feb; 21(2): 178-185.