Published online Sep 7, 2020. doi: 10.3748/wjg.v26.i33.4900
Peer-review started: April 30, 2020
First decision: June 13, 2020
Revised: June 24, 2020
Accepted: August 20, 2020
Article in press: August 20, 2020
Published online: September 7, 2020
In the last years, several studies have been focused on elucidate the role of tumor microenvironment (TME) in cancer development and progression. Within TME, cells from adaptive and innate immune system are one of the main abundant components. The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth. This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Liver is well-known to be an important immunological organ with unique microenvironment. Here, in normal conditions, the rich immune-infiltrating cells cooperate with non-parenchymal cells, such as liver sinusoidal endothelial cells and Kupffer cells, favoring self-tolerance against gut antigens. The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells, in order to understand how this cross-talk promotes tumor growth. Deeper attention is, in fact, focused on immune-based therapy for these tumors, as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment. In this review, we will examine the key pathways underlying TME cell-cell communications, with deeper focus on the role of natural killer cells in primary liver tumors, such as HCC and iCCA, as new opportunities for immune-based therapeutic strategies.
Core tip: Natural killer (NK) cells are an important innate immune cell type with high cytotoxic activity, mainly involved in the clearance of virus-infected and tumor cells. Due to their potential anti-tumor activity, NK cells are gaining a deeper attention as a promising strategy for immune-based cancer therapy. Several studies reveal that both in hepatocellular carcinoma and intrahepatic cholangiocarcinoma, NK cells infiltrate within tumors and their high frequency was found to be related with a favorable overall survival in these patients. In this review, the authors summarize the current literature on NK cells and their role in primary liver tumors.