Cytotoxic immune cell-based immunotherapy for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common solid tumors with poor clinical prognosis. Novel therapeutic regimens are urgently required for patients with advanced HCC. Both pre-clinical and clinical studies suggest immunotherapy as an attractive alternative for advanced HCC treatment. Natural killer (NK) cells and CD8 + T cells are the most important cytotoxic immune cells involved in cancer treatment and elimination. Reinvigorating the anticancer activity of NK and CD8 + T cells is the fundamental guarantee for the success of immunotherapy in advanced HCC treatment. Therefore, in this review, we aim to summarize the characteristics and roles of NK and CD8 + T cells in HCC development, describe the frontiers of immunotherapy for advanced HCC based on immune checkpoint inhibitors and adoptive cell transfer, and discuss their limitations and scope for future improvement.

Natural Killer Cells and T Cells in Hepatocellular Carcinoma and Viral Hepatitis: Current Status and Perspectives for Future Immunotherapeutic Approaches

“…NK cells are considered as the first line of defense against viral infections and tumor invasion [16]. NK cells recognize and kill virus infected cells and tumor cells without major histocompatibility complex restriction or prior sensitization, via cytotoxicity or cytokine secretion [58,59]. NK cells are known for their ability to rapidly recognize and clear viral-infected, tumor-transformed, and stressed cell targets in the absence of antigen specificity [60,61].…”

“…NK cells in human are phenotypically defined as CD3 − CD56 + large granular lymphocytes. NK cells express acti-vating receptors such as CD16, NKp30, NKp44, NKp46, NKp80, NKG2D, CD244, CD226; cytokine receptors such as IL-2R, IL-28R, IL-12R, IFNR, IL-15R, IL-18R, IL-1R8, IL-10R, and TGFβR [58,62]. The inhibitory receptors expressed by NK cells include NKG2A, KLRG1, KIRs, TIGIT, TIM3, Siglecs, PD-1, LAG3, A2AR, LAIRs, and ILTs [58,63].…”

“…NK cells express acti-vating receptors such as CD16, NKp30, NKp44, NKp46, NKp80, NKG2D, CD244, CD226; cytokine receptors such as IL-2R, IL-28R, IL-12R, IFNR, IL-15R, IL-18R, IL-1R8, IL-10R, and TGFβR [58,62]. The inhibitory receptors expressed by NK cells include NKG2A, KLRG1, KIRs, TIGIT, TIM3, Siglecs, PD-1, LAG3, A2AR, LAIRs, and ILTs [58,63]. Under homeostatic conditions, human circulating NK cells represent about 5-15% of circulating lymphocytes and are subdivided into two main subsets defined based on their differential expression of CD56 and CD16, namely CD56 bright CD16 − and CD56 dim CD16 + [64,65].…”

Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

“…NK cells represent a major target to improve cancer immunotherapies. Four major axis are currently widely studied to take advantage of NK cell function in cancer treatment [38,[222][223][224][225][226]. These include (i) the production and infusion of engineered NK cells into patients, (ii) the use of agonistic or blocking antibodies targeting NK cells, (iii) NK cell stimulation with cytokines and (iv) the targeting of the tumor microenvironment leveraging NK cell function [222] (Figure 3).…”