Perspectives on the Neoadjuvant Use of Immunotherapy in Hepatocellular Carcinoma
Abstract
Immune checkpoint inhibitor (ICI) therapy is an increasingly used treatment modality across the various stages of hepatocellular cancer (HCC). There is currently no standard peri-operative therapy for HCC, despite a high probability of recurrence. Emerging studies in a variety of tumors demonstrate significant pathologic and immune responses to neoadjuvant immunotherapy. Unlike kinase inhibitors and other targeted therapies, which demonstrated no benefit in the adjuvant setting and fail to induce significant responses, ICIs can induce radiologically appreciable reduction in disease burden, which make ICI combinations an appealing downstaging strategy in patients early or locally advanced disease. Additionally, induction of anti-tumor immunity in the pre-operative setting may induce protracted T-cell response that, in the post-operative phase, may be capable of eliminating micro-metastatic disease and prevent future recurrence. In this review, we discuss the rationale and clinical hurdles that underlie optimal integration of immunotherapy in the pre-operative setting, highlighting the positive impact on surgical and oncological outcomes in patients with early-stage HCC.
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PD-L1 is widely expressed in various malignancies.
“Programmed death ligand 1 (PD-L1, namely CD274) is widely expressed in various malignancies”
From PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells (2022) · cites this paper as [3]
PD-L1 induces immune evasion by targeting PD-1 on activated T cells, resulting in T cell exhaustion.
“induces immune evasion by targeting its ligand, programmed cell death 1 (PD-1) on activated T cells, resulting in T cell exhaustion1–4.”
From PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells (2022) · cites this paper as [3]
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Immunotherapies for hepatocellular carcinoma
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Self-citationNeoadjuvant clinical trials provide a window of opportunity for cancer drug discovery
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Self-citation
- Authors
- Pinato, D. J., Fessas, P., Sapisochin, G., & Marron, T. U.
- Affiliations
- Hammersmith Hospital (GB)
- Multi‐Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Toronto General Hospital, Department of Surgery,University of Toronto,Toronto,Canada
- Mount Sinai Hospital (US)
- Corresponding author
- Pinato, David J.
- Venue
- Hepatology
- Published
- 2021-06-28
- Volume
- 74
- Issue
- 1
- Pages
- 483-490
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W3114582868
- Cited by
- 74
- References
- 44
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 18 · 2023: 12 · 2022: 25 · 2021: 9
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Wellcome Trust (P3416)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- hepatocellular carcinoma, neoadjuvant immunotherapy, immune checkpoint inhibitors, downstaging, early-stage HCC, recurrence prevention, antitumor immunity, T cell response
- MeSH terms
- Antineoplastic Agents, Immunological, Progression-Free Survival, Immune Checkpoint Inhibitors, Antineoplastic Combined Chemotherapy Protocols, Hepatectomy, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Neoplasm Recurrence, Local, Randomized Controlled Trials as Topic, Chemotherapy, Adjuvant, Disease-Free Survival, Neoadjuvant Therapy, Protein Kinase Inhibitors
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