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PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma.

ABSTRACT: BACKGROUND:CD8+ T cells differentiate into exhausted status within tumors, including hepatocellular carcinoma (HCC), which constitutes a solid barrier to effective anti-tumor immunity. A detailed characterization of exhausted T cells and their prognostic value in HCC is lacking. METHODS:We collected fresh tumor tissues with adjacent non-tumor liver tissues and blood specimens of 56 HCC patients, as well as archived samples from two independent cohorts of HCC patients (n?=?358 and n?=?254), who underwent surgical resection. Flow cytometry and multiplex immunostaining were used to characterize CD8+ T cells. Patient prognosis was evaluated by Kaplan-Meier analysis and Cox regression analysis. RESULTS:CD8+ T cells were classified into three distinct subpopulations: PD1Hi, PD1Int and PD1-. PD1Hi CD8+ T cells were significantly enriched in tumor compared to adjacent non-tumor liver tissues. PD1Hi CD8+ T cells highly expressed exhaustion-related inhibitory receptors (TIM3, CTLA-4, etc.) and transcription factors (Eomes, BATF, etc.). In addition, PD1Hi CD8+ T cells expressed low levels of cytotoxic molecules and displayed a compromised capacity to produce pro-inflammatory cytokines while the expression of anti-inflammatory IL-10 was up-regulated following mitotic stimulation. Furthermore, PD1Hi CD8+ T cells shared features with tissue resident memory T cells and were also characterized in an aberrantly activated status with an apoptosis-prone potential. In two independent cohorts of HCC patients (n?=?358 and n?=?254), we demonstrated that PD1Hi or TIM3+PD1Hi CD8+ T cells were significantly correlated with poor prognosis, and the latter was positioned in close proximity to PD-L1+ tumor associated macrophages. CONCLUSION:The current study unveils the unique features of PD1Hi CD8+ exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies.

SUBMITTER: Ma J

PROVIDER: S-EPMC6884778 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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PD1<sup>Hi</sup> CD8<sup>+</sup> T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma.

Ma Jiaqiang J Zheng Bohao B Goswami Shyamal S Meng Lu L Zhang Dandan D Cao Chunmei C Li Teng T Zhu Fangming F Ma Lijie L Zhang Zhao Z Zhang Shuhao S Duan Meng M Chen Qin Q Gao Qiang Q Zhang Xiaoming X

Journal for immunotherapy of cancer 20191129 1

<h4>Background</h4>CD8<sup>+</sup> T cells differentiate into exhausted status within tumors, including hepatocellular carcinoma (HCC), which constitutes a solid barrier to effective anti-tumor immunity. A detailed characterization of exhausted T cells and their prognostic value in HCC is lacking.<h4>Methods</h4>We collected fresh tumor tissues with adjacent non-tumor liver tissues and blood specimens of 56 HCC patients, as well as archived samples from two independent cohorts of HCC patients (n ...[more]

PMID: 31783783

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Dataset Information

PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma.

Publications

PD1<sup>Hi</sup> CD8<sup>+</sup> T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma.

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