| Title: |
Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer |
| Authors: |
Roesel R.; Strati F.; Basso C.; Epistolio S.; Spina P.; Djordjevic J.; Sorrenti E.; Villa M.; Cianfarani A.; Mongelli F.; Galafassi J.; Popeskou S. G.; Facciotti F.; Caprera C.; Melle F.; Majno-Hurst P. E.; Franzetti-Pellanda A.; De Dosso S.; Bonfiglio F.; Frattini M.; Christoforidis D.; Iezzi G. |
| Contributors: |
Roesel, R; Strati, F; Basso, C; Epistolio, S; Spina, P; Djordjevic, J; Sorrenti, E; Villa, M; Cianfarani, A; Mongelli, F; Galafassi, J; Popeskou, S; Facciotti, F; Caprera, C; Melle, F; Majno-Hurst, P; Franzetti-Pellanda, A; De Dosso, S; Bonfiglio, F; Frattini, M; Christoforidis, D; Iezzi, G |
| Publisher Information: |
Taylor and Francis Ltd.; US |
| Publication Year: |
2025 |
| Collection: |
Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| Subject Terms: |
Immune cell gene profiling; intratumoral microbiota; LARC; nCRT; predictive signature |
| Description: |
Locally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefit from additional treatments to increase CR rates. Reliable predictive markers are lacking. Aim of this study was to identify novel signatures predicting nCRT responsiveness. We performed a combined analysis of tumor-associated microbiome and immune gene expression profiling of diagnostic biopsies from 70 patients undergoing nCRT followed by rectal resection, including 16 with CR and 54 with non-CR. Findings were validated by an independent cohort of 49 patients, including 7 with CR and 42 with non-CR. Intratumoral microbiota significantly differed between CR and non-CR groups at genus and species level. Colonization by bacterial species of Ruminococcus genera was consistently associated with CR, whereas abundance of Fusobacterium, Porhpyromonas, and Oscillibacter species predicted non-CR. Immune gene profiling revealed a panel of 59 differentially expressed genes and significant upregulation of IFN-gamma and -alpha response in patients with CR. Integrated microbiome and immune gene profiling analysis unraveled clustering of microbial taxa with each other and with immune cell-related genes and allowed the identification of a combined signature correctly identifying non-CRS in both cohorts. Thus, combined intratumoral microbiome-immune profiling improves the prediction of response to nCRT. Correct identification of unresponsive patients and of bacteria promoting responsiveness might lead to innovative therapeutic approaches based on gut microbiota pre-conditioning to increase nCRT effectiveness in LARC. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39992705; info:eu-repo/semantics/altIdentifier/wos/WOS:001431919900001; volume:14; issue:1; journal:ONCOIMMUNOLOGY; https://hdl.handle.net/10281/550726 |
| DOI: |
10.1080/2162402X.2025.2465015 |
| Availability: |
https://hdl.handle.net/10281/550726; https://doi.org/10.1080/2162402X.2025.2465015 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative Commons ; license uri:http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.EED5D0E |
| Database: |
BASE |