Unlocking Immunotherapy: Insights into Treating Rare Eye Cancer

New research from the University of Pittsburgh sheds light on why conventional immunotherapies struggle to combat metastatic uveal melanoma and highlights the efficacy of adoptive therapy, where a patient’s T cells are grown outside the body and then reintroduced. Published in Nature Communications, the study also introduces a novel clinical tool for predicting patient response to adoptive therapy, offering insights to enhance personalized treatments and avoid ineffective interventions for this aggressive cancer.
Dr. Udai Kammula, senior author and associate professor of surgery at Pitt, along with his team at the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center, challenges the notion that uveal melanoma is immune-resistant. They reveal that while T cells do infiltrate metastatic tumors, they remain dormant due to tumor-induced suppression. Adoptive therapy rescues these suppressed cells, enabling successful treatment in select patients.
Unlike cutaneous melanoma, which responds well to immune checkpoint inhibitors, uveal melanoma has proven resilient to conventional immunotherapies. Through their earlier study in Lancet Oncology, Kammula’s team demonstrated promising results with adoptive therapy, with 35% of patients experiencing partial or complete cancer regression. However, the underlying reasons for the ineffectiveness of immune checkpoint inhibitors remained unclear.
To address this gap, the researchers leveraged a comprehensive repository of uveal melanoma samples and associated clinical data. Analyzing metastases from 84 patients, they discovered abundant T cells within tumors. Single-cell RNA sequencing of nearly 100,000 cells further revealed that while these T cells were activated and capable of attacking tumors, they were suppressed within the tumor microenvironment, hindering their proliferation.
To guide treatment decisions, Kammula and lead author Dr. Shravan Leonard-Murali developed the Uveal Melanoma Immunogenic Score (UMIS), a composite measure reflecting the tumor’s immune activity based on over 2,000 gene expressions. Patients with higher UMIS scores showed improved responses to adoptive therapy, indicating UMIS’ potential as a predictive biomarker.
Moreover, patients with UMIS scores above a certain threshold exhibited better progression-free and overall survival rates, suggesting UMIS’ utility in treatment selection and prognosis assessment. Kammula emphasizes UMIS’ dynamic nature, offering insights into optimal treatment timing and patient selection.
Ongoing clinical trials at Pitt are evaluating UMIS’ predictive value in real-time, underscoring its potential to guide personalized treatment strategies. Kammula’s team aims to extend their findings beyond uveal melanoma to address other challenging cancers like pancreatic cancer, developing a pan-cancer UMIS to predict adoptive therapy responses across cancer types.

Leave a Reply

Your email address will not be published. Required fields are marked *