Tumor Genomic Testing Guides Immunotherapy Selection in Pituitary Tumors

Recurrence and resistance create an urgent need for treatment strategies aligned with tumor biology. Molecular profiling can reveal immune-evasion pathways that conventional regimens may miss. New findings demonstrate a genomics-guided immunotherapy approach achieving complete remission in an aggressive pituitary tumor.

At the University of Cincinnati Gardner Neuroscience Institute’s Brain Tumor Center, researchers used tumor genomic testing to identify a mismatch repair alteration and match a patient with an appropriate immunotherapy clinical trial. The approach is advanced as a precision strategy for pituitary carcinomas (PCs) and aggressive pituitary adenomas (APAs), which have historically shown poor responses to standard care. The findings were published on May 1, 2026, in Surgical Neurology International, with a related letter to Pituitary in July 2025 advocating broader access to immunotherapy for APAs and PCs.

The team describes how some cancer cells express proteins that suppress immune surveillance; immunotherapy regimens can block these proteins, restoring antitumor activity. Unlike historical cytotoxic agents that broadly target dividing cells, these “precision” therapies can, in select cases, act against tumor-associated molecular vulnerabilities. Based on these observations, the investigators encourage routine tumor genomic testing in PCs and APAs to guide consideration of immunotherapy as a potential first-line option.

The single-patient case study began with visual loss due to a pituitary mass. Gross-total resection restored vision, and adjuvant radiation maintained remission for about one year. After multifocal recurrence progressed despite first-line temozolomide, tumor genomics revealed a mismatch repair mutation, enabling enrollment in an immunotherapy clinical trial; the patient achieved a complete response that persisted after therapy was discontinued.

Following the initial report, three additional patients worldwide with aggressive pituitary tumors or pituitary carcinomas have been confirmed to achieve complete responses after immunotherapy. The research emphasizes DNA testing of pituitary tumors—specifically to detect mismatch repair alterations—as a gateway to appropriate immunotherapy trials. Future work at the center will apply the same test-and-treat paradigm to glioblastoma, with a planned Phase 1 trial incorporating navigated focused ultrasound to facilitate blood–brain barrier transit of the immunotherapy regimen.

“To date, immunotherapy has revolutionized the care of patients with metastatic melanoma and non-small cell lung cancer, but until recently, they hadn't been available for patients with aggressive pituitary cancer,” said Jonathan Forbes, MD, associate professor and residency program director in the Department of Neurosurgery, University of Cincinnati College of Medicine.

“Following a thorough review of tumor genomics, we were able to get the patient signed up for the right clinical trial. Using that scientifically-informed regimen, he was able to clear the cancer. The double vision completely resolved on the immunotherapy regimen. It was the first in the world to have a complete response, meaning the cancer completely vanished and did not return after the medication was stopped,” said Dr. Forbes

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University of Cincinnati Gardner Neuroscience Institute