A study in head and neck cancer of OX40 expression on tumor infiltrating T-cells compared to those in the blood indicated that, while OX40 was more highly expressed on tumor resident Tregs, it was elevated to a lesser extent on tumor infiltrating conventional CD4s.33 Preclinical studies have shown depletion of TLS-associated Tregs can increase rates of proliferation of CD4+ and CD8 + T-cells in TLSs 5-fold and 10-fold, respectively.34 OX40 antibodies, targeted to deplete TLS-associated OX40+ Tregs, could be an approach to expand response rates to anti-PD-(L)1 therapies. This evidence concerns the gene CD8A and head and neck cancer.