Paper - Review

DOI: 10.1016/j.ccell.2021.10.009

Graphical abstract

In brief

❗: the largest NSCLC cohort
→ analyzed ← by 1⃣ scRNA-seq 2⃣ CITE-seq
∴ Shared & variable elements ← of the treatment-naïve immune response
∴ Independent immune-modifying effects of 1⃣ tumor mutational burden 2⃣ TP53 mutation
∴ A refined model of how 1⃣ neoantigens 2⃣ driver mutations 3⃣ immune state
→ combine to drive immunotherapeutic response

Highlights

⭐: scRNA-seq of immune cells ← in 35 NSCLCs
→ reveals activation module

⭐: CITE-seq
→ validates & extends scRNA-seq-based cell annotations

⭐: LCAM is associated
← with 1⃣ tumor mutational burden 2⃣ ectopic antigens 3⃣ driver mutations

⭐: LCAM
→ confers prognostic benefit
← in anti-PD-L1 treatment
← not in chemotherapy

Summary

Immunotherapy
→ a mainstay of NSCLC management

❗: tumor mutational burden
→ correlates ← with response to immunotherapy
❓: little is known
← about the relationship ← between 1⃣ the baseline immune response 2⃣ tumor genotype

Profiled 360K cells ← from 35 early-stage NSCLC lesions
∵ Using single-cell RNA sequencing

Identified a cellular module consisting
← of 1⃣ PDCD1+CXCL13+ activated T cells 2⃣ IgG+ plasma cells 3⃣ SPP1+ macrophages
∴ The lung cancer activation module (LCAM-hi)

❗: the confirmed LCAM-hi enrichment ← in multiple NSCLC cohorts
❗: Paired CITE-seq → established an antibody panel
→ to identify LCAM-hi lesions

LCAM presence → was found
→ to be independent of overall immune cell content
∴ Correlated ← with 1⃣ TMB 2⃣ cancer testis antigen 3⃣ TP53 mutations

High baseline LCAM scores
→ correlated ← with enhanced NSCLC response to immunotherapy
← even in patient with above median TMB
∴ Immune cell composition
→ may be a non-redundant biomarker ← of response to immunotherapy

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