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Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas.

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas.
Author Information (click to view)

Müller S, Agnihotri S, Shoger KE, Myers MI, Smith N, Chaparala S, Villanueva CR, Chattopadhyay A, Lee AV, Butterfield LH, Diaz A, Okada H, Pollack IF, Kohanbash G,


Müller S, Agnihotri S, Shoger KE, Myers MI, Smith N, Chaparala S, Villanueva CR, Chattopadhyay A, Lee AV, Butterfield LH, Diaz A, Okada H, Pollack IF, Kohanbash G, (click to view)

Müller S, Agnihotri S, Shoger KE, Myers MI, Smith N, Chaparala S, Villanueva CR, Chattopadhyay A, Lee AV, Butterfield LH, Diaz A, Okada H, Pollack IF, Kohanbash G,

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JCI insight 2018 04 053(7) doi 10.1172/jci.insight.98791

Abstract

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns.

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