Paper - Review

DOI: 10.1016/j.cell.2020.07.017

Graphical Abstract

In Brief

Analysis of (metastatic lung cancer biopsies)
← before & after targeted therapy
→ reveals 1⃣ molecular 2⃣ immune adaptations
← that shape clinical outcomes

Highlights

scRNA-seq
→ is feasible ← in metastatic human NSCLSc
→ reveals → a rich tumor ecosystem

1⃣ individual tumors 2⃣ cancer cells
→ exhibit substantial molecular diversity

1⃣ cancer 2⃣ tumor micro-environment cells
→ exhibit marked therapy-induced plasticity

scRNA-seq of metastatic NSCLCs
→ unveils new opportunities
→ to improve clinical outcomes

Summary

Lung cancer
← the leading cause of cancer mortality
→ exhibits heterogeneity
← that 1⃣ enables adaptability 2⃣ limits therapeutic success 3⃣ remains incompletely understood

scRNA-seq
← of metastatic lung cancer
→ was performed
← using 49 clinical biopsies obtained
← from 30 patients ← before & during targeted therapy

Over 20K cancer & TME single-cell profiles
→ exposed → a rich & dynamic tumor ecosystem

scRNA-seq of cancer cells
→ illuminated → targetable oncogenes
← beyond those detected clinically

Cancer cells surviving therapy
← as residual disease (RD)
→ expressed an alveolar-regenerative cell signature
∴ A therapy-induced primitive cell-state transition

Those
→ present ← at on-therapy progressive disease (PD)
→ up-regulated 1⃣ kynurenine 2⃣ plasminogen 3⃣ gap-junction pathways

1⃣ Active T-lymphocytes 2⃣ decreased macrophages
→ were present
← at 1⃣ RD 2⃣ immuno-suppressive cell states characterized PD

Biological features
← revealed by scRNA-seq
→ were biomarkers of clinical outcomes
← in independent cohorts

❗: how therapy-induced adaptation of the multi-cellular ecosystem
← of metastatic cancer shapes clinical outcomes

---