Preclinical study demonstrates that tumor-expressed HNF1A stimulates CD8+ T-cell activation in colon and lung cancer models, suggesting improved responses to immune checkpoint blockade.
The development of immune checkpoint inhibitors has improved the treatment outcomes for patients with many types of cancer. However, the clinical benefits remain limited in many patients, highlighting the need for novel therapeutic strategies to enhance antitumor immunity. Hepatocyte nuclear factor 1A (HNF1A) is a transcription factor that regulates the expression of several liver-specific genes, and its expression is increased in certain cancers, such as colon and non-small cell lung cancer (NSCLC), compared with normal tissue. However, the effects of HNF1A on antitumor immunity remain unknown. Here, we show that colon cancer and NSCLC expressing HNF1A activate antitumor immunity. HNF1A-overexpressing cancer cells activated T-cell-mediated anticancer cytotoxicity when co-cultured with peripheral blood mononuclear cell-derived T cells. In a syngeneic mouse model, MC38 colon adenocarcinoma growth was suppressed after subcutaneous injection of HNF1A-overexpressing cancer cells. Flow cytometry analysis of tumor-infiltrating T cells showed that CD8 + T cells increased and were functionally activated in tumors overexpressing HNF1A. Treatment with an anti-PD-1 monoclonal antibody reduced tumor growth in HNF1A-overexpressing tumors. These results suggest that HNF1A plays a role in antitumor immunity and may influence the response to immune checkpoint blockade.
No takes yet. Share an insight, caveat, or question.
Nakashima et al. (2026) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: