Page 121 - Read Online

Original Article | Open Access

Cancer Drug Resistance

Fang et al. Cancer Drug Resist. 2025;8:42 DOI:10.20517/cdr.2025.124

ROS1 mutations promote an immunosuppressive
tumor microenvironment via MYC to confer immune
evasion in head and neck cancer

Chao Fang 1,2,# , Qin Zhang , Rui Fang 1,2,# , Ying Li , Jing Bai , Xiaojing Huang , Jingting Lu , Dongsheng
1
1,2
1,2
1
3,#
Chen , Yanxiang Zhang , Zuhong Chen 1,2
3
3
Keywords:
Head and neck cancer, ICI
resistance, ROS1 mutation,
tumor microenvironment
Citation: Fang C, Zhang Q,
Fang R, Li Y, Bai J, Huang X,
Lu J, Chen D, Zhang Y,
Chen Z. ROS1 mutations
promote an
immunosuppressive tumor
microenvironment via MYC
to confer immune evasion in
head and neck cancer.
Cancer Drug Resist.
2025;8:42.
https://dx.doi.org/10.20517
/cdr.2025.124
Abstract
Received: 30 Jun 2025
First Decision: 31 Jul 2025 Aim: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; however, their
Revised: 13 Aug 2025 efficacy in head and neck cancer (HNC) remains limited, with only a minority of patients
Accepted: 14 Aug 2025 achieving durable responses. Understanding the molecular mechanisms underlying ICI
Published: 22 Aug 2025
resistance in HNC is therefore crucial.
Academic Editor:
Godefridus J. Peters Methods: We conducted an integrative analysis of genomic, transcriptomic, and clinical
Copy Editor: data from 139 ICI-treated HNC patients (MSKCC cohort) and 502 treatment-naïve HNC
Pei-Yun Wang
Production Editor: cases (TCGA cohort). ROS1 mutation status, tumor mutational burden (TMB), neoantigen
Pei-Yun Wang load, immune cell infiltration (via CIBERSORT), and immune-related gene expression were
evaluated. Gene set enrichment analysis (GSEA) was performed to identify dysregulated
pathways. Survival outcomes were assessed using Kaplan-Meier analysis and Cox
regression, with statistical significance defined as P <​ 0.05.

1 The School of Clinical Medicine, Fujian Medical University, Fuzhou 350000, Fujian, China.
2 Department of Otolaryngology-Head & Neck Surgery, The First Hospital of Putian, Putian 351100, Fujian, China.
3 State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing 210018, Jiangsu,
China. ‌
# Authors contributed equally.

Correspondence to: Prof. Zuhong Chen, The School of Clinical Medicine, Fujian Medical University, No. 88 Jiaotong Road, Fuzhou
350000, Fujian, China. E-mail: zuhongchen@126.com (lead contact); Dr. Yanxiang Zhang, State Key Laboratory of Neurology and
Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., No. 699-18 Xuanwu Street, Nanjing 210018, Jiangsu, China. E-mail:
yxzhang2008@hotmail.com

www.oaepublish.com Submit a Manuscript: https://ucenter.oaepublish.com
114