CD226 and melanoma: PD-1 and TIGIT double-positive T cells are predictive of enhanced anti-PD-1 activity as has been shown in melanoma and merkel cell carcinoma [37], but without the presence of DNAM-1 (marking the activation state of CD8+ T cells), there is no durable response to anti-PD-1 or indeed anti-TIGIT blockade (Fig. 1).