4.7 Article

TIGIT+ TIM-3+ NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus-related hepatocellular carcinoma

Journal

ONCOIMMUNOLOGY
Volume 10, Issue 1, Pages -

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2021.1942673

Keywords

Hepatocellular carcinoma; Natural killer cells; TIGIT; TIM-3; co-expression

Funding

  1. Special Fund of Capital Health Research and Development [2020-2-2173]
  2. National Science Foundation of China [81874435, 81902895]
  3. Dengfeng Talent Support Program of Beijing Municipal Administration of Hospitals [DFL20191803]
  4. Fund for Beijing Science & Technology Development of Traditional Chinese Medicine [JJ-2020-52]
  5. Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support [ZYLX202127]
  6. National Natural Science Foundation of China

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Research has found that the co-expression of TIGIT and TIM-3 on NK cells is elevated in patients with HBV-HCC, leading to functional dysfunction that may be closely related to disease progression.
The prognosis of hepatocellular carcinoma (HCC) is extremely poor, of which hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) accounts for the majority in China. Immune checkpoint inhibitors have become an effective immunotherapy method for the treatment of HCC, but they are mainly used for T cells. NK cells play a vital role as the first line of defense against tumors. Therefore, we explored the characteristic expression pattern of immune checkpoints on NK cells of HBV-HCC patients. We analyzed the correlation between the co-expression of TIGIT and TIM-3 and the clinical progress of patients with HBV-HCC. The co-expression of TIGIT and TIM-3 on NK cells is elevated in patients with HBV-HCC. TIGIT(+)TIM-3(+)NK cells showed exhausted phenotypic characteristics and displayed dysfunction manifested as weakened killing function, reduced cytokine production, and proliferation function. TIGIT(+)TIM-3(+)NK cells participate in NK cells function exhaustion and are closely related to the disease progression of patients with HBV-HCC, suggesting a new target for future immunotherapy.

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