Checkpoint inhibitors (CPIs) un-do one of the mechanisms that cancers use to evade the immune system. Their success has proven the concept of using the body’s own defences to fight cancer, firing up the far broader field of immuno-oncology. But checkpoint inhibitors are reaching an impasse. It is now understood that they are effective only in the minority of tumors which already show a low level immune response. This is most likely to be the case in melanomas for example, with high numbers of gene mutations and thus multiple neo-antigens. Many more tumors are immunologically ‘cold’ – they have relatively fewer gene mutations and are therefore completely silent to the immune system, and to the effects of CPIs.
Combining CPIs with other tools that trigger an underlying immune response may vastly expand their efficacy and reach. Hence the...
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