Novel strategy of sirolimus plus thymalfasin and huaier granule on tumor recurrence of hepatocellular carcinoma beyond the UCSF criteria following liver transplantation: A single center experience.
Zhou. Lin L; Pan. Li-Chao LC; Zheng. Yong-Gen YG; Du. Guo-Sheng GS; Fu. Xiao-Qian XQ; Zhu. Zhi-Dong ZD; Song. Ji-Yong JY; Liu. Zhi-Jia ZJ; Su. Xiang-Zheng XZ; Chen. Wen W; Zheng. De-Hua DH; Suo. Long-Long LL; Yang. Shao-Zhen SZ
Key Findings
- Patients on sirolimus + thymosin‑alpha‑1 + huaier had significantly longer overall survival (5‑year OS 77.8%) and disease‑free survival (5‑year DFS 50%) than controls.
- Serum AFP levels and FoxP3+ regulatory T‑cell percentages dropped markedly in the treatment group during the first year post‑transplant.
- CD8+ T‑cell percentages rose, indicating a shift toward a more active anti‑tumor immune profile.
Practical Outcomes
- For those experimenting with immune‑modulating peptides, this study suggests thymosin‑alpha‑1 may help tilt the immune system away from tolerance (lower T‑regs) toward active tumor surveillance (higher CD8+ cells) when paired with sirolimus. However, the benefit was shown only in liver‑transplant patients with advanced HCC, so broader use remains unproven and should be approached cautiously.
Summary
A small retrospective study found that liver transplant patients with advanced liver cancer who received a combination of the drug sirolimus, the immune‑boosting peptide thymosin‑alpha‑1 (called thymalfasin), and a mushroom extract (huaier granule) lived longer without the cancer coming back compared to those on standard tacrolimus therapy. The combo also lowered cancer marker AFP and reduced suppressive T‑reg cells while boosting killer CD8+ T cells.
Abstract
Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18). The SRL+ group had significantly longer recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1-year: 100%, 3-year: 94.4%, 5-year: 77.8%; DFS, 1-year: 88.9%, 3-year: 55.6%, 5-year: 50.0%). Furthermore, compared with pre-LT values and the control group, the SRL+ group had significantly lower serum α-fetoprotein (AFP) levels (both P<0.0001) and percentage of Forkhead box P3 (FoxP3)<sup>+</sup> Treg lymphocytes (P<0.001) during the first year. In the SRL+ group, FoxP3<sup>+</sup>/cluster of differentiation (CD)8<sup>+</sup> Treg lymphocyte percentages decreased significantly following LT (P<0.001); however, CD8<sup>+</sup>/CD3<sup>+</sup> T-cells significantly increased (P<0.001). Levels of serum AFP and FoxP3<sup>+</sup> Treg cells increased when tumors relapsed, and decreased to near-normal when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and Treg levels, while increasing CD8<sup>+</sup> T cells, indicating an associated mechanism among them. In conclusion, SRL+ therapy appears to be safe and effective in preventing HCC recurrence following LT with no significant adverse events, and warrants further investigation.
Study Information
pubmed
2018
2018-07-27T00:00:00.000Z
10.3892/ol.2018.9226
16
48