Immunotherapy for hepatocellular carcinoma recurrence after liver transplantation, can we harness the power of immune checkpoint inhibitors?

Jiang, Jingxin; Huang, Haitao; Chen, Ruihan; Lin, Yimou; Ling, Qi

doi:10.3389/fimmu.2023.1092401

Cited by 12 publications

(8 citation statements)

References 101 publications

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“…Immunotherapies have revolutionized advanced HCC management, with their specific role in transplantation still evolving but promising [5 ▪▪ ,6,7 ▪▪ ,11–14,26–34,35 ▪▪ ,36 ▪ ,37,38 ▪ ,39 ▪ ,40–42,54–67,68 ▪ ,69 ▪ ].…”

Section: Discussionmentioning

confidence: 99%

“…The focus is on its role as a neoadjuvant regimen, downstaging patients outside of Milan criteria, and acting as a “bridge” to transplantation [6,7 ▪▪ ,13]. Furthermore, there remain limited data regarding its prospective use as an adjuvant strategy, encompassing posttransplant consolidation and as an alternative approach in managing disease recurrence [14].…”

Section: Introductionmentioning

confidence: 99%

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Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy

Tabrizian,

Zeitlhoefler,

Hassan

et al. 2023

Current Opinion in Organ Transplantation

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Purpose of review The increasing success of liver transplantation in hepatocellular carcinoma (HCC) drives an ever-evolving search for innovative strategies to broaden eligible patients’ pools. Recent advances in immuno-oncology have turned the spotlight on immune checkpoint inhibitors (ICIs). This review offers an updated overview of ICIs in liver transplantation for HCC, exploring neoadjuvant and adjuvant approaches and addressing unanswered questions on safety, patients’ selection, and response predictors. Recent findings ICIs have transitioned from being a last-chance therapeutic hope to becoming an integral cornerstone in the treatment of advanced HCC, holding great promise as a compelling option not only to downstage patients for transplantation but also as an alternative strategy in addressing posttransplantation disease recurrence. Despite ongoing refinements in immunotherapeutic agents, the complex molecular pathways involved emphasize the need for a comprehensive approach to integrate immunotherapy in liver transplantation. Summary Initial concerns about graft rejection, with ICIs as a bridging therapy to liver transplantation, were successfully addressed using adequate immunosuppressants strategies and minimized with a sufficient washout period. Post-liver transplantation disease recurrence remains challenging, requiring a balance between effective therapy and preserving graft function. Emphasis should be placed on clinical trials validating the risk-benefit ratio of ICIs for liver transplantation, guiding appropriate patients’ selection, and establishing clear management pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy

Tabrizian,

Zeitlhoefler,

Hassan

et al. 2023

Current Opinion in Organ Transplantation

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“…Indeed, evidence on this topic is scarce. A recent literature review including 27 cases of liver transplants with HCC recurrence treated with ICIs, 8 (29.6%) patients had disease control, but 6 (22.2%) patients developed acute graft rejection [ 25 ]. Therefore, the most suitable systemic therapy for HCC recurrence post liver transplant is still MTI.…”

Section: Lenvatinib Monotherapy As First-line Treatment In Advanced Hccmentioning

confidence: 99%

The evolving role of lenvatinib at the new era of first-line hepatocellular carcinoma treatment

Chan¹,

Chan²

2023

Clin Mol Hepatol

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Emergence of multi-targeted kinase inhibitors (MTIs) and immune checkpoint inhibitors (ICI) have changed the landscape of management in hepatocellular carcinoma (HCC). Combination therapy involving ICI has superseded sorafenib as the first-line treatment option for advanced HCC due to their superior response rates and survival benefits based on recently published phase III trials. However, the role of first-line lenvatinib remains uncertain as no prospective trials have compared its efficacy with ICI in advanced HCC. Several retrospective studies have shown that first-line lenvatinib may not be inferior to ICI combination. Indeed, a growing body of evidence suggests that ICI treatment is associated with inferior treatment outcome in non-viral HCC patients, questioning the supremacy of ICI treatment in all patients and rendering first-line lenvatinib as a potential preferred treatment option. Furthermore, in high-burden intermediate-stage HCC, accumulating evidence supports first-line lenvatinib, or in combination with transarterial chemoembolization (TACE), as a preferred treatment option over TACE alone. In this Review, we describe the latest evidence surrounding the evolving role of first-line lenvatinib in HCC.

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“…Activating cellular immunity by blocking immune checkpoints can have a therapeutic anti-tumor effect, and this therapeutic modality has been shown to produce long-lasting clinical responses. On the contrary, activation of immune checkpoint proteins usually causes suppression of the bodily immune response and induces the onset of immune tolerance, which can play a key role in treating autoimmune disorders or inducing transplantation immune tolerance, among other disease processes [7][8][9][10]. Therefore, immune checkpoint proteins are expected to play a unique role in disease treatment as part of new immunotherapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

LILRB4 Checkpoint for Immunotherapy: Structure, Mechanism and Disease Targets

Xiang,

Yin,

Wei

et al. 2024

Biomolecules

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LILRB4, a myeloid inhibitory receptor belonging to the family of leukocyte immunoglobulin-like receptors (LILRs/LIRs), plays a pivotal role in the regulation of immune tolerance. LILRB4 primarily mediates suppressive immune responses by transmitting inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs (ITIMs). This immune checkpoint molecule has gained considerable attention due to its potent regulatory functions. Its ability to induce effector T cell dysfunction and promote T suppressor cell differentiation has been demonstrated, indicating the therapeutic potential of LILRB4 for modulating excessive immune responses, particularly in autoimmune diseases or the induction of transplant tolerance. Additionally, through intervening with LILRB4 molecules, immune system responsiveness can be adjusted, representing significant value in areas such as cancer treatment. Thus, LILRB4 has emerged as a key player in addressing autoimmune diseases, transplant tolerance induction, and other medical issues. In this review, we provide a comprehensive overview of LILRB4, encompassing its structure, expression, and ligand molecules as well as its role as a tolerance receptor. By exploring the involvement of LILRB4 in various diseases, its significance in disease progression is emphasized. Furthermore, we propose that the manipulation of LILRB4 represents a promising immunotherapeutic strategy and highlight its potential in disease prevention, treatment and diagnosis.

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Immunotherapy for hepatocellular carcinoma recurrence after liver transplantation, can we harness the power of immune checkpoint inhibitors?

Cited by 12 publications

References 101 publications

Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy

Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy

The evolving role of lenvatinib at the new era of first-line hepatocellular carcinoma treatment

LILRB4 Checkpoint for Immunotherapy: Structure, Mechanism and Disease Targets

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