Dataset Information

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8⁺ T Cells in Hepatocellular Carcinoma.

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

TIGIT was enriched, whereas its co-stimulatory counterpart CD226 was down-regulated on PD1^high CD8⁺ TILs. PD1^high TIGIT⁺ CD8⁺ TILs co-expressed exhaustion markers TIM3 and LAG3 and demonstrated higher TOX expression. Furthermore, this subset showed decreased capacity to produce IFN-γ and TNF-α. Expression of TIGIT-ligand CD155 was up-regulated on tumor cells compared with hepatocytes in TFL. Whereas single PD1 blockade preferentially enhanced ex vivo functions of CD8⁺ TILs from tumors with PD1^high CD8⁺ TILs (high PD1 expressers), co-blockade of TIGIT and PD1 improved proliferation and cytokine production of CD8⁺ TILs from tumors enriched for PD1^int CD8⁺ TILs (low PD1 expressers). Importantly, ex vivo co-blockade of TIGIT/PD1 improved proliferation, cytokine production, and cytotoxicity of CD8⁺ TILs compared with single PD1 blockade.

Conclusions

Ex vivo, co-blockade of TIGIT/PD1 improves functionality of CD8⁺ 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.

SUBMITTER: Ge Z

PROVIDER: S-EPMC8255944 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8<sup>+</sup> T Cells in Hepatocellular Carcinoma.

Ge Zhouhong Z Zhou Guoying G Campos Carrascosa Lucia L Gausvik Erik E Boor Patrick P C PPC Noordam Lisanne L Doukas Michael M Polak Wojciech G WG Terkivatan Türkan T Pan Qiuwei Q Takkenberg R Bart RB Verheij Joanne J Erdmann Joris I JI IJzermans Jan N M JNM Peppelenbosch Maikel P MP Kraan Jaco J Kwekkeboom Jaap J Sprengers Dave D

Cellular and molecular gastroenterology and hepatology 20210327 2

<h4>Background & aims</h4>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).<h4>Methods</h4>Mononuclear leukocytes were isolated from tumors, paired tumor-free liver tissues (TFL) and peripheral blood of HCC patients, and u ...[more]

PMID: 33781741

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Dataset Information

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8⁺ T Cells in Hepatocellular Carcinoma.

Background & aims

Methods

Results

Conclusions

Publications

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8<sup>+</sup> T Cells in Hepatocellular Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8+ T Cells in Hepatocellular Carcinoma.

Background & aims

Methods

Results

Conclusions

Publications

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8<sup>+</sup> T Cells in Hepatocellular Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8⁺ T Cells in Hepatocellular Carcinoma.