RT Journal Article SR Electronic T1 Identification of FABP5 as an immunometabolic marker in human hepatocellular carcinoma JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP e000501 DO 10.1136/jitc-2019-000501 VO 8 IS 2 A1 Fangming Liu A1 Weiren Liu A1 Shuang Zhou A1 Chunhui Yang A1 Mengxin Tian A1 Guangshuai Jia A1 Han Wang A1 Bijun Zhu A1 Mingxiang Feng A1 Yan Lu A1 Tiankui Qiao A1 Xinxin Wang A1 Wei Cao A1 Xiangdong Wang A1 Yinghong Shi A1 Duojiao Wu YR 2020 UL http://jitc.bmj.com/content/8/2/e000501.abstract AB Background Regulating T-cell metabolism is crucial for their anticancer activity. Therefore, understanding the function and metabolism of human tumor-infiltrating T cells is of broad interest and clinical importance.Methods CD3+CD45+ T cells were sorted from adjacent area or tumor core of human hepatocellular carcinoma (HCC), then the clusters and heterogeneity of T cells were further interrogated by single-cell transcriptomic profiling. 118 surgical samples from patients with HCC were histologically examined for infiltration of CD8+ T cells in tumor and adjacent tissue.Results Single-cell transcriptomic profiling indicated that several exhausted T-cell (Tex) populations differentially coexisted in the tumor and adjacent tissue. CD137 identifies and enriches Tex with superior effector functions and proliferation capacity. Furthermore, enhanced fatty acid-binding protein 5 (FABP5) expression along with increased mitochondrial oxidative metabolism were evident in these CD137-enriched Tex. Inhibiting FABP5 expression and mitochondrial fatty acid oxidation impaired the anti-apoptosis and proliferation of CD137-enriched Tex. These observations have been verified by generating CD137 CART. Immunohistochemistry staining on the tissue microarray of 118 patients with HCC showed intra-tumoral FABP5 high CD8+ T-cell infiltration was linked to overall and recurrence-free survival.Conclusions The tumor microenvironment can impose metabolic restrictions on T-cell function. CD137, a costimulatory molecule highly expressed on some Tex, uses exogenous fatty acids and oxidative metabolism to mediate antitumor immunity. The immunometabolic marker FABP5 should be investigated in larger, longitudinal studies to determine their potential as prognostic biomarkers for HCC.