Abstract
The lack of PD-1 or LAG-3 mutants with constitutive inhibitory activities prevents a systematic approach to dissect all the intracellular events regulated by PD- 1 and LAG-3 that establish a strong T cell dysfunctionality in patients with intrinsic resistance to PD-1 therapies. It is thought that PD-1 and LAG-3 form a supramolecular complex together with TCR components in order to exert their inhibitory activity over TCR signal transduction. So far, no PD-1 and LAG-3 mutants with constitutive signalling activities have been described.
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