Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer

被引：20

作者：

Onder, Lucas ^{[1
]}

Papadopoulou, Chrysa ^{[1
]}

Lutge, Almut ^{[2
,3
]}

Cheng, Hung-Wei ^{[1
]}

Lutge, Mechthild ^{[1
]}

Perez-Shibayama, Christian ^{[1
]}

Gil-Cruz, Cristina ^{[1
]}

De Martin, Angelina ^{[1
]}

Kurz, Lisa ^{[1
]}

Cadosch, Nadine ^{[1
]}

Pikor, Natalia B. ^{[1
,4
]}

Rodriguez, Regulo ^{[5
]}

Born, Diana ^{[5
]}

Jochum, Wolfram ^{[5
]}

Leskow, Pawel ^{[6
]}

Dutly, Andre ^{[6
]}

Robinson, Mark D. ^{[2
,3
]}

Ludewig, Burkhard ^{[1
,7
,8
,9
]}

机构：

[1] Inst Immunobiol, Kantonsspital St Gallen, CH-9007 St Gallen, Switzerland

[2] Univ Zurich, Dept Mol Life Sci, CH-8057 Zurich, Switzerland

[3] Univ Zurich, SIB Swiss Inst Bioinformat, CH-8057 Zurich, Switzerland

[4] Swiss Fed Inst Technol, Inst Microbiol & Immunol, CH-8093 Zurich, Switzerland

[5] Inst Pathol, Kantonsspital St Gallen, CH-9007 St Gallen, Switzerland

[6] Dept Thorac Surg, Kantonsspital St Gallen, CH-9007 St Gallen, Switzerland

[7] Univ Hosp Zurich, Univ Heart Ctr, CH-8091 Zurich, Switzerland

[8] Univ Zurich, CH-8091 Zurich, Switzerland

[9] Univ Hosp Zurich, Ctr Translat & Expt Cardiol, CH-8091 Zurich, Switzerland

来源：

CELL | 2025年 / 188卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

TERTIARY LYMPHOID STRUCTURES; B-CELLS; MIGRATION; IMMUNITY; ENTRY; IMMUNOTHERAPY; VISUALIZATION; PRECURSORS; REVEALS;

D O I：

10.1016/j.cell.2024.10.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Stringent control of T cell activity in the tumor microenvironment is essential for the generation of protective antitumor immunity. However, the identity, differentiation, and functions of the cells that create critical fibroblastic niches promoting tumor-infiltrating T cells remain elusive. Here, we show that CCL19-expressing fibroblastic reticular cells (FRCs) generate interconnected T cell environments (TEs) in human non-small cell lung cancer, including tertiary lymphoid structures and T cell tracks. Analysis of the FRC-T cell interactome in TEs indicated molecular networks regulating niche-specific differentiation of CCL19-expressing fibroblasts and T cell activation pathways. Single-cell transcriptomics and cell fate-mapping analyses in mice confirmed that FRCs in TEs originate from mural and adventitial progenitors. Ablation of intratumoral FRC precursors decreased antitumor T cell activity, resulting in reduced tumor control during coronavirus vector-based immunotherapy. In summary, specialized FRC niches in the tumor microenvironment govern the quality and extent of antitumor T cell immunity.

引用

页码：430 / +

页数：37

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