Resident Immune Cells of the Liver in the Tumor Microenvironment

Abstract

The liver is a central immunomodulator that ensures a homeostatic balance between protection and immunotolerance. A hallmark of hepatocellular carcinoma (HCC) is the deregulation of this tightly controlled immunological network. Immune response in the liver involves a complex interplay between resident innate, innate, and adaptive immune cells. The immune response in the liver is modulated by its continuous exposure to toxic molecules and microorganisms that requires a degree of immune tolerance to protect normal tissue from damage. In HCC pathogenesis, immune cells must balance a dual role that includes the elimination of malignant cells, as well as the repair of damaged liver tissue to maintain homeostasis. Immune response in the innate and adaptive immune systems extends to the cross-talk and interaction involving immune-regulating non-hematopoietic cells, myeloid immune cells, and lymphoid immune cells. In this review, we discuss the different immune responses of resident immune cells in the tumor microenvironment. Current FDA-approved targeted therapies, including immunotherapy options, have produced modest results to date for the treatment of advanced HCC. Although immunotherapy therapy to date has demonstrated its potential efficacy, immune cell pathways need to be better understood. In this review article, we summarize the roles of specific resident immune cell subsets and their cross-talk subversion in HCC pathogenesis, with a view to identifying potential new biomarkers and therapy options.

Immune Checkpoint Blockade: A Strategy to Unleash the Potential of Natural Killer Cells in the Anti-Cancer Therapy

“…Tactile/CD96 is another important IC for NK cell effector functions, which shares with TIGIT the ligands. CD96 + NK cells are significantly increased in the intra-tumor tissues of hepatocellular carcinoma (HCC) [ 35 , 36 ]. CD96 + NK cells are functionally impaired with reduced capacity to release IFN-γ and TNF-α, and low gene expression levels of Tbx21 , Prf1 , and GzmB .…”

Effects of dexmedetomidine on oxidative stress, programmed cell death, liver function, and expression of peripheral immune cells in patients with primary liver cancer undergoing hepatectomy

“…The induction of proinflammatory cytokine and chemokines (interleukin-2) is detrimental among primary liver cancer patients who have undergone hepatectomy ( Sachdeva et al, 2015 ; Sachdeva and Arora, 2020 ; Cai et al, 2022 ; Chen et al, 2022 ; Lu et al, 2022 ). From the observations above, we could conclude that Dexmedetomidine could be a potential agent against the progression of primary liver cancer.…”

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“…Moreover, the liver produces immune-related molecules such as C-reactive protein and soluble pattern-recognition receptors, which play a key role in systemic inflammation and immunity ( Figure 2 ). 28

Figure 2 Immune microenvironment of liver metastases Schematic representation of the interactions between cancer cells, various immune cells, and soluble factors that mediate these cellular interactions. Arrows and blunt ends indicate promotion and inhibition, respectively.

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“…It is necessary that the liver maintains a level of tolerance that balances the elimination of bacterial pathogens and avoids excessive inflammation caused by the nonpathogenic intestinal environment, thus resulting in a unique immunotolerant microenvironment. 28 …”