TY - JOUR T1 - Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-000987 VL - 8 IS - 2 SP - e000987 AU - Harry Ho Man Ng AU - Ren Yuan Lee AU - Siting Goh AU - Isabel Shu Ying Tay AU - Xinru Lim AU - Bernett Lee AU - Valerie Chew AU - Huihua Li AU - Benedict Tan AU - Sherlly Lim AU - Jeffrey Chun Tatt Lim AU - Bijin Au AU - Josh Jie Hua Loh AU - Sahil Saraf AU - John Edward Connolly AU - Tracy Loh AU - Wei Qiang Leow AU - Joycelyn Jie Xin Lee AU - Han Chong Toh AU - Fabio Malavasi AU - Ser Yee Lee AU - Pierce Chow AU - Evan W Newell AU - Su Pin Choo AU - David Tai AU - Joe Yeong AU - Tony Kiat Hon Lim Y1 - 2020/08/01 UR - http://jitc.bmj.com/content/8/2/e000987.abstract N2 - Introduction Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality globally. Immune-checkpoint blockade (ICB) is one of the systemic therapy options for HCC. However, response rates remain low, necessitating robust predictive biomarkers. In the present study, we examined the expression of CD38, a molecule involved in the immunosuppressive adenosinergic pathway, on immune cells present in the tumor microenvironment. We then investigated the association between CD38 and ICB treatment outcomes in advanced HCC.Methods Clinically annotated samples from 49 patients with advanced HCC treated with ICB were analyzed for CD38 expression using immunohistochemistry (IHC), multiplex immunohistochemistry/immunofluorescence (mIHC/IF) and multiplex cytokine analysis.Results IHC and mIHC/IF analyses revealed that higher intratumoral CD38+ cell proportion was strongly associated with improved response to ICB. The overall response rates to ICB was significantly higher among patients with high proportion of total CD38+cells compared with patients with low proportion (43.5% vs 3.9%, p=0.019). Higher responses seen among patients with a high intratumoral CD38+cell proportion translated to a longer median progression-free survival (mPFS, 8.21 months vs 1.64 months, p=0.0065) and median overall survival (mOS, 19.06 months vs 9.59 months, p=0.0295). Patients with high CD38+CD68+macrophage density had a better mOS of 34.43 months compared with 9.66 months in patients with low CD38+CD68+ macrophage density. CD38hi macrophages produce more interferon γ (IFN-γ) and related cytokines, which may explain its predictive value when treated with ICB.Conclusions A high proportion of CD38+ cells, determined by IHC, predicts response to ICB and is associated with superior mPFS and OS in advanced HCC. ER -