Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients

Abstract

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.

Cellular Senescence in Liver Cancer: How Dying Cells Become “Zombie” Enemies

“…The authors demonstrated that the mRNA expression of EZH2, G6PD, LGALS3, and PSMD14 senescence-related genes was elevated in cancer tissues from HCC patients compared with normal gastric cancer parietal tissues, suggesting that these genes may act as potential biomolecular markers for the prognosis and stratification of HCC patients. Similarly, immune senescence profiles have been shown to possibly predict HCC prognosis in liver transplant patients [128]. Overall, the realization of a prognostic model for cellular senescence risk score can not only be exploited to predict HCC patients' prognosis, but can also provide more strategies for the clinical treatment of HCC patients.…”

Ferroptosis in liver cancer: a key role of post-translational modifications

“…Approximately three-quarters to four-fifths of patients diagnosed with primary liver cancer have HCC. Characterized by rapid progression, high metastasis potential, and late diagnosis at advanced stages, HCC often has a poor prognosis due to high recurrence rates after surgery or other treatments ( 5 ).…”

“…potential, and late diagnosis at advanced stages, HCC often has a poor prognosis due to high recurrence rates after surgery or other treatments (5).…”