Hhla2 Novel Member Of The B7 Family Of Inhibitory Ligands, Is Highly Expressed In Osteosarcoma

Purpose: Over the past four decades there have been minimal improvements in outcomes for patients with osteosarcoma (OS). New targets and novel therapies are needed to improve outcomes for these patients. In this study, we sought to evaluate the prevalence and prognostic utility of the immune checkpoint inhibitor HHLA2 in OS. Experimental Design: HHLA2 expression was evaluated in two cohorts of OS patients using a tumor microarray (TMA) (n = 62) and whole slides (n = 48). HHLA2 expression was assessed in primary tumor specimens and metastatic disease, and correlated with the presence of tumor infiltrating lymphocytes (TILs), and event free survival. Results: HHLA2 was expressed in 68% of OS tumors in the TMA and in 54% in the second cohort. HHLA2 was expressed in almost all metastatic disease specimens and was more prevalent than in primary specimens without known metastases (93% vs 53%, p = 0.02). TILs were present in 75% of all osteosarcoma specimens. Patients whose tumors were ≥25% or ≥50% HHLA2 positive had significantly worse five-year event-free-survival (33% vs 64%, p = 0.03 and 14% vs 59%, p = 0.02). Conclusions: HHLA2 is expressed in the majority of OS tumors, is associated with metastatic disease, and is associated with poorer survival. Further studies are needed assessing the effect of HHLA2 expression on the function of the immune microenvironment, as well as assessing the feasibility and utility of targeting HHLA2 in OS. Citation Format: Pratistha Koirala, Michael Roth, Jonathan Gill, Jordan Chinai, Michelle Ewart, Sajida Piperdi, David Geller, Bang Hoang, Yekaterina Fatakhova, Maya Ghorpade, Xingxing Zang, Richard Gorlick. HHLA2, a novel member of the B7 family of inhibitory ligands, is highly expressed in osteosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2221.