Clinical and Immunological Features of Primary Enteric-Type Thymic Adenocarcinomas: A Rare Variant of a Rare Cancer
JTO Clinical and Research Reports, 2026
Sivapiromrat A., McAdams M., Donahue R., Celades C., Lassoued W., Bagheri H., Bahiru E., Swift S., Feierabend C., Sansone S., DaSilva L., Szabo E., Zhao C., Schlom J., Gulley J., Rajan A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology | Pathophysiology Patient Stratification | Serum |  Olink Target 96 |
Abstract
Background
Primary thymic adenocarcinomas are a rare subtype of thymic carcinoma, which share morphological and immunohistochemical features with gastrointestinal cancers. The immunological features of thymic adenocarcinoma remain poorly understood and optimal treatment strategies have not been established.
Methods
In this single-institution retrospective study, we identified seven patients with enteric-type thymic adenocarcinoma. Clinical characteristics, histopathology, and molecular profiles were analyzed. Comprehensive immune profiling was conducted using peripheral blood mononuclear cells (PBMCs) and archival tumor tissue. The PBMC immune profile was compared with non-adenocarcinoma thymic epithelial tumors and with samples obtained from healthy donors.
Results
Enteric-type thymic adenocarcinomas exhibit aggressive clinical behavior and respond poorly to systemic therapy, including immune checkpoint inhibitors. Genomic analyses revealed frequent TP53 mutations, a marker of poor prognosis for thymic epithelial tumors. Immune analyses in PBMCs showed higher levels of effector T cell subsets, including CD4+ and CD8+ T cell subsets and lower levels of immunosuppressive cell populations compared with other thymic epithelial tumors. Higher levels of serum analytes related to angiogenesis, cell proliferation and growth were detected. Tumor immune profiling showed features of an immune-desert phenotype.
Conclusions
Enteric-type thymic adenocarcinomas are immunologically cold tumors that are enriched in peripheral immune markers reflective of cell proliferation and angiogenesis. The immunological profile appears distinct from other thymic epithelial tumors and provides a potential explanation for the aggressive nature of the disease. If validated in other studies, these findings can potentially inform the development of optimal systemic therapies for this rare variant of thymic carcinoma.