Clinicopathological analysis of CD8-positive lymphocytes in the tumor parenchyma and stroma of hepatocellular carcinoma

Abstract

Tumor-infiltrating lymphocytes may be a manifestation of antitumor immunity. In the present study, hepatocellular carcinoma (HCC) and pericancerous non-tumor liver tissues samples were obtained from 86 surgical patients who had not received preoperative treatment. The cellular expression levels of CD4 and CD8 were immunohistochemically examined in the two tissue groups using tissue microarrays, to evaluate their clinicopathological relevance. Immunohistochemically, CD4 and CD8 T cells were observed in the tumor parenchyma and tumor stroma, and the intensity of CD4 and CD8 immunoreactivity was homogeneous in all HCC samples examined. Morphometrically, the average numbers of CD4- and CD8-positive T cells were significantly increased in the tumor stroma, compared with those in the tumor parenchyma (tumor stroma versus tumor parenchyma: 22±3.6 versus 7.4±0.9 in CD4, 32.8±4.2 versus 16±2.5 in CD8; both P<0.01). Furthermore, the average numbers of CD8-positive T cells in the tumor parenchyma and stroma were significantly increased, compared with the average numbers of CD4-positive cells (P<0.05). In addition, in the tumor parenchyma and stroma, the average numbers of CD8 T cells were significantly higher in patients with tumor diameters ≤5 cm compared with those in patients with tumor diameters >5 cm (diameter ≤5 cm versus diameter >5 cm: 18.1±3.3 versus 12.2±3.8 in tumor parenchyma, 36.5±4.8 versus 21.9±8.9 in tumor stroma; both P<0.05). In addition, CD8 expression was significantly enhanced in patients with chronic hepatitis and cirrhosis, compared with paired tumor parenchymal tissues (P<0.01). Furthermore, a significant positive correlation was observed between CD4 and CD8 expression in the tumor parenchyma and stroma (both P<0.001). These observations suggest that tumor parenchyma- or stroma-infiltrating CD8 T cells may be involved in HCC tumor diameter control.

Things fall apart with hepatocellular carcinoma and direct-acting antivirals

“…Moreover, the relationship between inflammation and HCC should be also evaluated because the immune system is important in the tumor microenvironment. For example, it was shown that CD8 expression was significantly increased in the peritumor chronic hepatitis and cirrhotic parenchymas, compared with those in paired tumor parenchymas [19]. This finding is concurrent with the results of a study revealing that the proportion of immunesuppressed regulatory T cells was significantly higher in HCC than that in the nontumorous liver.…”

Expression and Prognostic Value of Tumor-Infiltrating Lymphocytes and PD-L1 in Hepatocellular Carcinoma

“…The CD4+T/CD8+T ratio is crucial for the immune response and immune regulation; its changes reflect the immune state. 12 , 13 Some studies have found that lower CD8+TILs levels are related to some clinicopathological parameters, such as negative HBsAg, large tumor size, and late TNM stage. In addition, the high-density CD8+TILs have been related to better OS and DFS.…”

Preoperative prediction of hepatocellular carcinoma with portal vein tumor thrombus based on conventional data

“…A dramatic fall in the CD4 + T lymphocyte level greatly influenced the anti-tumor activity that may lead to a fast progression of HCC. Second, with the support of perforin and granzyme, CD8 + cytotoxic T lymphocytes (CTLs) can directly contact and kill tumor cells [ 35 ]. There is persuasive evidence that the depletion of CTLs may promote the invasion of tumor cells into the surrounding tissue and metastasis to new body sites; collectively, an increased number of CTLs in HCC is closely connected to a reduced tumor diameter and longer survival times [ 36 , 37 ].…”