The interactions between major immune effector cells and Hepatocellular Carcinoma: A systematic review

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common liver neoplasm with high morbidity and mortality. Tumor immunotherapy might be promising adjuvant therapy for HCC after surgery. To better develop HCC immunotherapy, comprehensive understanding of cell-cell interactions between immune effector cells and HCC cells remains crucial.

Aim: To review the existing studies to summarize the cell-cell interactions between major immune effector cells and HCC cells providing new data for HCC immunotherapy.

Methods: A systematic review was conducted by searching PubMed database covering all papers published in recent five years up to January 2020. The guidelines of the preferred reporting items for systematic reviews were firmly followed.

Results: There are 9 studies researching the interactions between CD8⁺ T lymphocytes and HCC cells and 22 studies researching that between natural killer (NK) cells and HCC cells. Among the 9 studies, 6 studies reported that CD8⁺ T lymphocytes showed cytotoxicity towards HCC cells while 3 studies found CD8⁺ T lymphocytes were impaired by HCC cells. Among the 22 studies, 20 studies presented that NK cells could inhibit HCC cells. Two studies were found to report NK cell dysfunction in HCC.

Conclusion: Based on the systematic analysis, we concluded that CD8⁺ T lymphocytes and NK cells can inhibit HCC cells. While in turn, HCC cells can also result in the dysfunction of those effector cells through various mechanisms. Organoids and direct contact cell co-culture with primary HCC cells and TILs should be the most innovative way to investigate the interactions and develop novel immunotherapy.

Keywords: CD8(+) T lymphocytes; Cytotoxicity; Dysfunction; Hepatocellular carcinoma; Natural Killer cells.