Immune atlas of pituitary neuroendocrine tumors highlights endocrine-driven immune signature and therapeutic implication.

Summary

Mass cytometry across 56 pitNETs reveals that hormone secretion status governs immune composition: functioning tumors are T cell–enriched with immunosuppressive markers (CD38, PD-1, PD-L1), correlating with shorter PFS. In primary cultures, combining PD-1 blockade with tumor-targeted therapy synergistically increases apoptosis, induces cell-cycle arrest, and suppresses hormone secretion.

Key Findings

• PitNETs show sparse immune infiltration overall; macrophages and T cells dominate.
• Functioning pitNETs are T cell–enriched with high CD38, PD-1, and PD-L1 expression, linked to shorter progression-free survival.
• PD-1 blockade combined with tumor-targeted therapy synergistically enhances apoptosis, induces cell-cycle arrest, and suppresses hormone secretion in primary cultures.

Clinical Implications

Suggests stratifying pitNETs by hormone secretion and immune markers to guide immunotherapy; supports clinical testing of PD-1 blockade combined with tumor-targeted therapies in functioning pitNETs.

Limitations

• Observational profiling without in vivo clinical trial validation
• Cohort size may not capture all pitNET subtypes; ex vivo synergy requires clinical confirmation

Future Directions

Prospective trials testing PD-1 blockade plus targeted agents in functioning pitNETs; development of predictive biomarkers and spatial multi-omics to refine patient selection.