RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP e000987
DO 10.1136/jitc-2020-000987
VO 8
IS 2
A1 Harry Ho Man Ng
A1 Ren Yuan Lee
A1 Siting Goh
A1 Isabel Shu Ying Tay
A1 Xinru Lim
A1 Bernett Lee
A1 Valerie Chew
A1 Huihua Li
A1 Benedict Tan
A1 Sherlly Lim
A1 Jeffrey Chun Tatt Lim
A1 Bijin Au
A1 Josh Jie Hua Loh
A1 Sahil Saraf
A1 John Edward Connolly
A1 Tracy Loh
A1 Wei Qiang Leow
A1 Joycelyn Jie Xin Lee
A1 Han Chong Toh
A1 Fabio Malavasi
A1 Ser Yee Lee
A1 Pierce Chow
A1 Evan W Newell
A1 Su Pin Choo
A1 David Tai
A1 Joe Yeong
A1 Tony Kiat Hon Lim
YR 2020
UL http://jitc.bmj.com/content/8/2/e000987.abstract
AB 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.