Impact of immunosuppressants on tumor pulmonary metastasis: new insight into transplantation for hepatocellular carcinoma

Cancer Biol Med. 2024 Dec 24;21(11):1033-1049. doi: 10.20892/j.issn.2095-3941.2024.0267.

Abstract

Pulmonary metastasis is a life-threatening complication for patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). In addition to the common mechanisms underlying tumor metastasis, another inevitable factor is that the application of immunosuppressive agents, including calcineurin inhibitors (CNIs) and rapamycin inhibitors (mTORis), after transplantation could influence tumor recurrence and metastasis. In recent years, several studies have reported that mTORis, unlike CNIs, have the capacity to modulate the tumorigenic landscape post-liver transplantation by targeting metastasis-initiating cells and reshaping the pulmonary microenvironment. Therefore, we focused on the effects of immunosuppressive agents on the lung metastatic microenvironment and how mTORis impact tumor growth in distant organs. This revelation has provided profound insights into transplant oncology, leading to a renewed understanding of the use of immunosuppressants after LT for HCC.

Keywords: Liver transplantation; hepatocellular carcinoma; immunosuppressants; lung immune microenvironment; lung metastasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / surgery
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / secondary
  • Liver Neoplasms* / surgery
  • Liver Transplantation* / adverse effects
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • MTOR Inhibitors / pharmacology
  • MTOR Inhibitors / therapeutic use
  • Tumor Microenvironment / drug effects

Substances

  • Immunosuppressive Agents
  • MTOR Inhibitors

Grants and funding

This work was supported by the Major Research Plan of the National Natural Science Foundation of China (Grant No. 92159202), the Key Research & Development Plan of Zhejiang Province (Grant No. 2024C03051), the National Key Research and Development Program of China (Grant No. 2021YFA1100500), the National Natural Science Foundation of China (Grant No. 82303387), Natural Science Foundation of Zhejiang Province (Grant No. LQ23H160048).