Background: CD8+ T cells are critical for the oncogenesis and progression of the hepatocellular carcinoma (HCC) tumor microenvironment, receiving antigen signals from antigen-presenting cells and directly contributing to antitumor responses. Summary: CD8+ T cells mediate immunogenic cell death, facilitate immune signal transmission, and play a significant role in various treatments, including surgery, transarterial chemoembolization, and immunotherapy. Extensive research on the role of CD8+ T cells within the HCC microenvironment has shown considerable progress. Immunometabolic targets on CD8+ T cells have demonstrated potential in combination with immunotherapies for HCC; however, they have not yet reached the clinical trial stage. Key Messages: This review provides a comprehensive overview of recent research on immune and immunometabolic targets of CD8+ T cells within the HCC microenvironment. By highlighting advances and potential mechanisms, this review aims to support the development of effective clinical strategies in this field.

Alveolar echinococcosis (AE) is a life-threatening human disease caused by Echinococcus multilocularis transmitted between rodents and dogs/foxes in the Northern Hemisphere. The study aims to identify the genetic variation of the parasite in AE patients from China. E. multilocularis isolates were collected from wild small mammals (n = 6) and AE patients (n = 56) from western China. Genomic DNA was extracted from different tissue samples including paraffin tissue blocks, ethanol fixed tissues and frozen tissues surgically removed. Two mitochondrial gene fragments (526 bp for cob and 474 bp for nad2) of E. multilocularis were amplified and sequenced. The parasite fragment sequences of cob fragments from AE patients showed two haplotypes, and nad2 gene fragment sequences had four haplotypes. The gene sequences from Microtus sp. were 100% identical to the sequences of some isolates from AE patients. These haplotypes were distributed in both Qinghai and Xinjiang provinces. Alignment analysis with the sequences from the GenBank databases showed five genotypes including three Asian genotypes, one from Europe and one from North America. Most AE patients harbored the Asian genotype 1 which may be an indication of its relative frequency in the definitive hosts and the environment or of its pathogenicity to humans, which calls for further research.

Background: Alveolar echinococcosis (AE) is caused by the larval stage ofEchinococcus multilocularis(E. multilocularis), and considered as public health issue. Parasite-host immune interaction is pivotal during infection. As a subset of innate lymphoid cells, NK cells are known to play an important role during virus, bacteria, intra/extracellular parasitic infections and tumor progression. However, the possible role of NK cells inE. multilocularisinfection in both human and murine is little known. Herein, the functional alteration of hepatic NK cells and their related molecules inE. multilocularisinfected mice were studied.Methods: 2000 protoscoleces (PSCs) were injected to C57BL/6 mice via the portal vein to establish secondaryE. multilocularisinfection.NK cells population and their related molecules (CD69, Ly49D, Ly49G2, Ly49H, Ly49I, NKG2A, NKG2D, granzyme B, IFN-γ, TNF-α) were assessed by using fluorescence-activated cell sorter (FACS) techniques and qRT-PCR. NK cell depletion was performed for further understanding the possible function of NK cells during infection.Results: The total frequencies of NK cells and NK-derived IFN-γ production were significantly reduced at designated time points (2, 4, 12 weeks). The liver resident (CD49a⁺DX5⁻) NK cells are decreased at 4 weeks after inoculation and which is significantly lower than in control mice. Moreover, in vivo antibody-mediated NK cell depletion increased parasitic load and decreased peri-parasitic fibrosis. Expression of the inhibitory receptor NKG2A was negatively related to NK- derived IFN-γ secretion.Conclusions: Our study showed down regulates of NK cells and upper regulates of NKG2A expression on NK cells duringE. multilocularisinfection. Reduction of NK cell frequencies and increased NKG2A might result in low cytotoxic activity through decreased IFN-γ secretion inE. multilocularisinfection. This result might be helpful to restore NK cell related immunity againstE. multilocularisinfection to treat alveolar echinococcosis.