1001P PD1midKLRG1+Tbethigh effector memory T in the peripheral blood correlates with tumor response to combined therapy with lenvatinib and anti-PD-1 antibodies in unresectable hepatocellular carcinoma

Abstract

Combination therapy of anti-angiogenic therapy and anti-PD-1antibody had shown promising anti-tumor effects for advanced hepatocellular carcinoma (HCC) in clinical trials. Despite the remarkable effect of combined therapy with lenvatinib and anti-PD-1 antibodies in HCC, most patients do not respond to the combination therapy, or develop resistance. Predicting tumor responses to the combination therapy is an important unmet need. Patients with advanced unresectable HCC received Lenvatinib 8 mg/d regardless of patient body weight and anti-PD-1 antibody either q2wk (nivolumab or camrelizumab) or q3wk (pembrolizumab, sintilimab or toripalimab). Patients who completed at least one efficacy and safety assessment were eligible for this study. High-dimensional single-cell mass cytometry (CyTOF) and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets was used to identify T cell subsets in the peripheral blood of patients before the treatment. From May 2019 to Dec. 2019, we recruited 15 patients. All the patients are assessable for efficacy. Two patients achieved complete response (CR), 7 patients achieved partial response (PR), and 6 patients achieved progressing disease (PD) per mRECIST. CyTOF identified 36 meta-clusters contained all of the major immune cell populations such as T cells, B cells, NK cells, DC cells and momocytes with a panel of 42 antibodies. Moreover, we delineated an PD1midKLRG1+Tbethigh effector memory T cell phenotype that was significantly more abundant in responders (CR or PR, n=9) to combined therapy compared with non-responders (n=6) (PD, P < 0.05). PD1midKLRG1+Tbethigh effector memory T cell in the peripheral blood may be a useful biomarker for predicting tumor response to the combination therapy in HCC.