2026-04-22 メモリアル・スローン・ケタリングがんセンター（MSKCC）
Tumor cells (red) actively engage neighboring cells (green) to create a local environment that supports tumor growth, a new study from the lab of MSK’s Dr. Joo-Hyeon Lee shows. The findings could eventually help doctors to better detect and treat cancer in its early stages.
＜関連情報＞
- https://www.mskcc.org/news/catching-cancers-earliest-moments-how-mutated-cells-transform-their-local-environment-so-tumor-can-develop
- https://www.nature.com/articles/s41586-026-10399-6
初期の線維化ニッチは腫瘍発生を許容する微小環境を形成する Early fibrotic niches establish tumour-permissive microenvironments
Erik C. Cardoso,Hyeyoung Lee,Frances J. England,Hyunjin Cho,Robin Lu,Sagar S. Varankar,Moo Suk Park,Natasha Rekhtman,Bon-Kyoung Koo,Benjamin D. Simons,Jinwook Choi &Joo-Hyeon Lee
Nature Published:22 April 2026
DOI:https://doi.org/10.1038/s41586-026-10399-6
Abstract
Pathologic transformation represents a critical yet poorly defined window during which mutant epithelial stem cells actively construct the microenvironment that enables tumour initiation1,2. Here using integrated single-cell, spatial and functional analyses, we define the earliest multicellular events that licence this transition following oncogenic activation in the lung. KrasG12D-mutant alveolar type II cells rapidly adopt regenerative-like states that act as signalling hubs, orchestrating coordinated stromal and immune reprogramming while enhancing epithelial plasticity. Through secretion of amphiregulin, mutant epithelial cells activate EGFR signalling in adjacent fibroblasts, inducing a fibrotic, injury-like programme. Reprogrammed fibroblasts, in turn, expand and reprogramme alveolar macrophages, amplifying inflammatory signalling and reinforcing epithelial plasticity. These reciprocal interactions establish a self-sustaining epithelial–stromal–immune circuit that generates a tumour-permissive niche before malignant outgrowth. Disruption of the amphiregulin–EGFR axis prevents early niche formation and abrogates tumour initiation. Conservation of this programme in KRASG12D-inducible human alveolar organoids and early-stage lung adenocarcinoma tissues identifies epithelial–microenvironment communication as a therapeutically actionable vulnerability and suggests that intercepting niche formation may prevent progression to treatment-resistant disease.
