Distinct CD8 T cell dynamics associate with response to neoadjuvant cancer immunotherapies.

🤖 Plain-English Summary

We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Anti-PD-1+LAG-3, but not anti-PD-1+CTLA-4, induces widespread TCR sharing among the different transcriptional states, as well as increased TCR diversity in responding patients.

🔑 Key Findings

• Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival.
• To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize transcriptional and proteomic dynamics of CD8 tumor-infiltrating lymphocytes (TILs) in a clonal manner.
• Anti-PD-1+LAG-3 reprograms CD8 TIL with type-I interferon response and exhaustion gene programs into effector memory and resident memory (T/T).

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