Paper - Review

DOI: 10.1038/s43018-021-00292-8

Abstract

❗: Anti-PD-1 treatment
→ has shown unprecedented clinical success
← in the treatment of NSCLC

❓: The underlying mechanisms
→ remain incompletely understood

Performed → 1⃣ temporal single-cell RNA 2⃣ paired T-cell receptor sequencing
← on 47 tumor biopsies ← from 36 patients with NSCLC
← following PD-1-based therapies

Observed → increased levels of precursor exhausted T cells (Texp)
→ in responsive tumors after treatment
← characterized ← by 1⃣ low expression of co-inhibitory molecules 2⃣ high expression of GZMK

Non-responsive tumors
→ failed → to accumulated Texp cells

Texp cells
→ were unlikely → to be derived ← from the re-invigoration of terminally exhausted cells
→ were accumulated ← by 1⃣ local expansion 2⃣ replenishment ← by peripheral T-cells
← with 1⃣ new 2⃣ pre-existing clonotypes

∴ 1⃣ Mechanisms → underlying PD-1-based therapies
2⃣ Implicating (clonal revival) & (expansion of Texp cells)

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