Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/191051
Title: | Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells |
Author: | Batlle, Eduard Cañellas Socias, Adrià Cortina, Carme Hernando Momblona, Xavier Palomo Ponce, Sergio Mulholland, Eoghan J. Turón, Gemma Mateo, Lidia Conti, Sefora Roman, Olga Sevillano, Marta Slebe, Felipe Stork, Diana Caballé Mestres, Adrià Berenguer Llergo, Antoni Álvarez Varela, Adrián Fenderico, Nicola Novellasdemunt, Laura Jiménez Gracia, Laura Sipka, Tamara Bardia, Lidia Lorden, Patricia Colombelli, Julien Heyn, Holger Trepat Guixer, Xavier Tejpar, Sabine Sancho, Elena Tauriello, Daniele V. F. Leedham, Simon Attolini, Camille Stephan-Otto |
Keywords: | Càncer colorectal Metàstasi Colorectal cancer Metastasis |
Issue Date: | 9-Nov-2022 |
Publisher: | Nature Publishing Group |
Abstract: | Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years1. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a unique tumour cell population that we named high-relapse cells (HRCs). We established a human-like mouse model of microsatellite-stable CRC that undergoes metastatic relapse after surgical resection of the primary tumour. Residual HRCs occult in mouse livers after primary CRC surgery gave rise to multiple cell types over time, including LGR5+ stem-like tumour cells2-4, and caused overt metastatic disease. Using Emp1 (encoding epithelial membrane protein 1) as a marker gene for HRCs, we tracked and selectively eliminated this cell population. Genetic ablation of EMP1high cells prevented metastatic recurrence and mice remained disease-free after surgery. We also found that HRC-rich micrometastases were infiltrated with T cells, yet became progressively immune-excluded during outgrowth. Treatment with neoadjuvant immunotherapy eliminated residual metastatic cells and prevented mice from relapsing after surgery. Together, our findings reveal the cell-state dynamics of residual disease in CRC and anticipate that therapies targeting HRCs may help to avoid metastatic relapse.© 2022. The Author(s), under exclusive licence to Springer Nature Limited. |
Note: | Postprint del document publicat a: https://doi.org/10.1038/s41586-022-05402-9 |
It is part of: | Nature, 2022, vol. 611, p. 603–613 |
URI: | http://hdl.handle.net/2445/191051 |
Related resource: | https://doi.org/10.1038/s41586-022-05402-9 |
ISSN: | 1476-4687 |
Appears in Collections: | Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Cañellas-Socias_Nature_2022_FULL.pdf | 175.69 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.