The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma

Authors

Dapeng Hao
Guangchun Han
Ansam Sinjab
Lorena Isabel Gomez-Bolanos
Rossana Lazcano
Alejandra Serrano
Sharia D Hernandez
Enyu Dai
Xuanye Cao
Jian Hu
Minghao Dang
Ruiping Wang
Yanshuo Chu
Xingzhi Song
Jianhua Zhang
Edwin R Parra
Jennifer A Wargo
Stephen G Swisher
Tina Cascone
Boris Sepesi
Andrew P Futreal
Mingyao Li
Steven M Dubinett
Junya Fujimoto
Luisa M Solis Soto
Ignacio I Wistuba
Christopher S Stevenson
Avrum Spira
Shabnam Shalapour
Humam Kadara
Linghua Wang

Publication Date

11-2-2022

Journal

Cancer Discovery

Abstract

Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they are poorly characterized. We performed paired single-cell RNA and B-cell receptor (BCR) sequencing of 16 early-stage LUADs and 47 matching multiregion normal tissues. By integrative analysis of ∼50,000 TIBs, we define 12 TIB subsets in the LUAD and adjacent normal ecosystems and demonstrate extensive remodeling of TIBs in LUADs. Memory B cells and plasma cells (PC) were highly enriched in tumor tissues with more differentiated states and increased frequencies of somatic hypermutation. Smokers exhibited markedly elevated PCs and PCs with distinct differentiation trajectories. BCR clonotype diversity increased but clonality decreased in LUADs, smokers, and with increasing pathologic stage. TIBs were mostly localized within CXCL13+ lymphoid aggregates, and immune cell sources of CXCL13 production evolved with LUAD progression and included elevated fractions of CD4 regulatory T cells. This study provides a spatial landscape of TIBs in early-stage LUAD.

Keywords

Humans, Plasma Cells, Ecosystem, Lung Neoplasms, Adenocarcinoma of Lung, Adenocarcinoma, Prognosis

Comments

Supplementary Materials

PMID: 36098652