The Pediatric Neurosurgery ImmunoOncology Laboratory (PNIO) at the University of Pittsburgh, under the direction of Gary Kohanbash, PhD, seeks to develop novel immuno-oncology approaches to treat deadly pediatric central nervous system tumors. With over a decade of experience in translational brain tumor immunology and involvement in numerous clinical trials, the laboratory has a specific focus on high-grade and low-grade gliomas, and ependymomas.
It is now known that immune cells can traffic into the central nervous system (CNS) and mediate anti-tumor responses. However, owing to its immune-privileged status and delicate brain structures, safety and efficacy must be considered in a different manner than tumors occurring outside of the CNS. With significant developments in next-generation sequencing, novel targets targeting pediatric CNS tumors are being identified.
The PNIO seeks to bridge the gaps between bioinformatics, preclinical studies, and patient care. Specific emphasis in the PNIO involve improving peptide vaccine immunotherapy through the following projects:
- Identification of novel targetable tumor antigens and neoantigens.
- Employing combination therapies using checkpoint inhibitors such as anti-PD1 and anti-TIGIT with peptide vaccine immunotherapy.
- Understanding how tumor genetics create a hostile environment for T-cell responses at the tumor site.
- Enhancing expression of molecules that make the tumor visible to the immune system.
- Non-invasive immunoPET of activated T-cells and Tumor-Associate Myeloid Cells (TAMCs) during IO therapy.
- Identification of biomarkers for CNS IO clinical trials.
- Single-cell RNA-sequencing to identify immune-cell and tumor cross-talk.
Selected Recent Publications
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. Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas. JCI Insight 5;3(7), 2018.
Chheda Z, Kohanbash G, Okada K, Jahan N, Sidney J, Pecoraro M, Carrera D, Shrivastav S, Liu S, Lin Y, Downey K, Chuntova P, Watchmaker P, Mueller S, Pollack I, Rajalingam R, Carcasboso A, Mann M, Sette A, Hou Y, Okada H. Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy. J Exp Med215(1):141-157, 2018.
Kohanbash G, Carrera DA, Shrivastav S, Ahn BJ, Jahan N, Mazor Tali, Chheda ZS, Downey Kira M, Watchmaker PB, Beppler C, Warta R, Amankulor NA, Herold-Mende C, Costello JF, Okada H. IDH mutations suppress STAT1 and CD8+ T-cell accumulation in gliomas. J Clin Invest 127(4):1425-1437, 2017.
Müller S, Kohanbash G, Liu JS, Alvarado B, Carrera D, Bhaduri A, Watchmaker P, Yagnik G, Di Lullo E, Malatesta M, Amankulor NM, Kriegstein AR, Lim D, Aghi MK, Okada H, Diaz A. Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment. Genome Biol 18(1):234, 2017.