Full Text

Turn on search term navigation

© 2023 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background

Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).

Methods

603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.

Results

T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.

Conclusions

The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

Details

Title
Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases
Author
Zhang, Chong 1 ; Xiang-Yu, Wang 2 ; Jie-Liang Zuo 3 ; Xue-Fu, Wang 4 ; Xiao-Wen, Feng 4 ; Zhang, Bo 2 ; Yi-Tong, Li 2 ; Chen-He, Yi 2 ; Zhang, Peng 2 ; Xiao-Chen, Ma 2 ; Zhen-Mei, Chen 2 ; Ma, Yue 2 ; Jia-Hao, Han 2 ; Bao-Rui, Tao 2 ; Zhang, Rui 2 ; Tian-Qi, Wang 1 ; Li, Tong 1 ; Wang, Gu 1 ; Si-Yu, Wang 1 ; Xiao-Fei, Zheng 1 ; Wen-Kang, Yuan 1 ; Zi-Jie Kan 1 ; Fan, Jie 5 ; Xiang-Yang, Hu 6 ; Li, Jun 3 ; Zhang, Chao 1 ; Jin-Hong, Chen 2   VIAFID ORCID Logo 

 Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China 
 Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China 
 Department of General Surgery, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China 
 School of Pharmacy, Anhui Medical University, Hefei, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China 
 Department of Pathology, Huashan Hospital Fudan University, Shanghai, China 
 Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China 
First page
e006425
Section
Immunotherapy biomarkers
Publication year
2023
Publication date
Feb 2023
Publisher
BMJ Publishing Group LTD
e-ISSN
20511426
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2774560897
Copyright
© 2023 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.