Page 127 - Read Online

Fang et al. Cancer Drug Resist. 2025;8:42 Page 7 of 13

Figure 3. Association of ROS1 mutations with TMB, neoantigen levels, and patient survival in HNC. Boxplots comparing log2-transformed
TMB between ROS1-Mut and ROS1-WT tumors in (A) MSKCC HNC cohort and (B) TCGA HNC cohort; (C) Boxplot comparing
log2-transformed neoantigen levels in TCGA HNC tumors by ROS1 mutation status; (D) Kaplan-Meier analysis of OS stratified by ROS1
mutation status and TMB levels. TMB: Tumor mutational burden; HNC: head and neck cancer; ROS1-Mut: ROS1 mutations; ROS1-WT:
ROS1-wild-type; TCGA: The Cancer Genome Atlas; OS: overall survival.

DISCUSSION
This study demonstrates that ROS1-Mut tumors develop an immunosuppressive TME, characterized by
diminished CD8 T cell infiltration, downregulation of key immune-related genes (e.g., CXCL9/10, IFNG,
+
PD-L1), and impaired interferon-γ (IFN-γ) signaling. These findings identify ROS1 mutation as a potential

120