Single-cell chromatin maps of thymic carcinoma reveal a conserved malignant state and its immunosuppressive dependencies

Using single-cell ATAC sequencing of three tumors and two adjacent normal tissues, we constructed a chromatin accessibility atlas of thymic carcinoma microenvironment and identified a recurrent tumor cell cluster, T3, shared across all patients. T3 showed consistent chromatin accessibility features at potential therapeutic targets (KIT, FGFR3, SYK), together with an inferred cancer-related regulatory program involving ELF2, BCLAF1, PBX3, IKZF1, NFKB1, TFDP2, and POU2AF1.

We also observed an immunosuppressive microenvironment characterized by exhausted CD8⁺ T-cell like and M2-like macrophages, both contributing to immune evasion. CD8⁺ T cells exhibited progressive activation of exhaustion-associated transcription factors and upregulation of CCL3 and CSF1, which may facilitate myeloid recruitment and dysfunction. Together, these data provide a single-cell chromatin resource for thymic carcinoma and nominate malignant and immune-associated programs for future validation.