Publications by authors named "Tarek Azar"
Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism in humans remains unclear. Here, we perform paired single-cell RNA and T cell receptor (TCR) sequencing across time in 36 patients with stage IV melanoma treated with anti-PD-1, anti-CTLA-4, or combination therapy.
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- Exhausted CD8 T cells in chronic viral infections and cancer express inhibitory receptors (IRs) like PD-1, which can be blocked to reinvigorate T cell function.
- Co-targeting multiple IRs, such as PD-1 and LAG-3, can enhance T cell response and disease control beyond blocking PD-1 alone.
- The study reveals distinct functions of PD-1 and LAG-3 in T cell activity, showing LAG-3's role in T cell durability and in creating a subset of T cells that are more effective at killing cancer or infected cells.