TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8+ T Cells in Hepatocellular Carcinoma
Zhouhong Ge, Guoying Zhou, Lucia Campos Carrascosa, Erik Gausvik, Patrick P.C. Boor, Lisanne Noordam, Michael Doukas, Wojciech G. Polak, Türkan Terkivatan, Qiuwei Pan, R. Bart Takkenberg, Joanne Verheij, Joris I. Erdmann, Jan N.M. IJzermans, Maikel P. Peppelenbosch, Jaco Kraan, Jaap Kwekkeboom, Dave Sprengers
Abstract
BACKGROUND & AIMS: TIGIT is a co-inhibitory receptor, and its suitability as a target for cancer immunotherapy in HCC is unknown. PD1 blockade is clinically effective in about 20% of advanced HCC patients. Here we aim to determine whether co-blockade of TIGIT/PD1 has added value to restore functionality of HCC tumor-infiltrating T cells (TILs). METHODS: Mononuclear leukocytes were isolated from tumors, paired tumor-free liver tissues (TFL) and peripheral blood of HCC patients, and used for flow cytometric phenotyping and functional assays. CD3/CD28 T-cell stimulation and antigen-specific assays were used to study the ex vivo effects of TIGIT/PD1 single or dual blockade on T-cell functions. RESULTS: TILs compared with single PD1 blockade. CONCLUSIONS: TILs that do not respond to single PD1 blockade. Therefore co-blockade of TIGIT/PD1 could be a promising immune therapeutic strategy for HCC patients.