Targeting Tumor‐Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies

Lu, Ligong; Jiang, Jun; Zhan, Meixiao; Zhang, Hui; Wang, Qian Ting; Sun, Sheng Nan; Guo, Xiao; Yin, Hua; Wei, Yadong; Li, Shi You; Liu, Jun O.; Li, Yong; He, You Wen

doi:10.1002/hep.31502

Cited by 30 publications

(36 citation statements)

References 94 publications

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“…According to reports, hepatocellular carcinoma has the third-highest rate of somatic mutations, showing a promising immunotherapy prospect [7][8][9]. However, the detection of TMB in HCC patients still has great limitations, such as high cost and long test cycle, requiring a large number of tumor cells to be tested.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

LRP1B mutation: a novel independent prognostic factor and a predictive tumor mutation burden in hepatocellular carcinoma

Liu¹,

Hou²,

Liang³

et al. 2021

J. Cancer

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Hepatocellular carcinoma (HCC) is one of the most common malignancies globally and the second leading cause of cancer-related death. Low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is one of the commonly mutated genes in HCC, but its role in HCC remains unclear. In this study, we analyzed the role of LRP1B mutation in HCC. The bioinformatics results show that LRP1B had a frequency of mutation in HCC patients, and LRP1B mutation was associated with a higher tumor mutation burden (TMB), and survival analysis proved that the prognosis of HCC patients with LRP1B mutation was poor. Univariate and multivariate COX regression analysis indicated that LRP1B mutation was an independent risk factor in evaluating HCC patients' prognosis. Correlation analysis showed that LRP1B mutation status was associated with the infiltration of 2 types of immune cells and higher expression of immune checkpoint gene human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) in HCC patients. In summary, the results show that LRP1B mutation is associated with the higher TMB and poor prognosis of patients with HCC, and it was an independent risk factor for clinical outcomes of HCC patients. LRP1B gene mutations can serve as predictors in HCC patients with higher TMB and higher expression of HHLA2. The results of this study will be beneficial to future studies on targeted therapy and immunotherapy for HCC.

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Section: Ivyspring International Publishermentioning

confidence: 99%

LRP1B mutation: a novel independent prognostic factor and a predictive tumor mutation burden in hepatocellular carcinoma

Liu¹,

Hou²,

Liang³

et al. 2021

J. Cancer

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“…First, most of the recovered COVID-19 patients may still need vaccination to prevent reinfection after 6 months or more. Second, an effective vaccine needs to engage all arms (B cell, CD4 T and CD8 T cells) of the adaptive immune response using a three-pronged vaccine design strategy (Lu et al, 2020a).…”

Section: Humoral Responses To Sars-cov-2 Infection In Covid-19 Patientsmentioning

confidence: 99%

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Zhang

Zhan

et al. 2020

Sci. China Life Sci.

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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

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“…While mutated neoantigens are rarely presented on HCC cells (33), TAAs such as alpha-fetoprotein (AFP), glypican-3 (GPC-3) or New York esophageal squamous cell carcinoma-1 (NY-ESO-1) are oftentimes overexpressed in HCC and phagocytosed by APCs (34,35). Nevertheless, DCs are often unable to effect successful T cell cross-priming, with multiple underlying FIGURE 1 | Principles of in situ vaccines.…”

Section: Liver and Hcc Immunologymentioning

confidence: 99%

“…As the induction of ICD alone mostly fails to create an effective antitumor response due to insufficient antigen or danger signal release (233), the development of higher-order combination protocols to ensure additional recruitment and activation of APCs as well as the overcoming of the immunosuppressive TME represents the key to success (35). The downside of these approaches might be a more frequent occurrence of immune-related adverse events (irAEs) (234).…”

Section: Perspectives and Pitfallsmentioning

confidence: 99%

In Situ Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular Carcinoma

et al. 2021

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Hepatocellular Carcinoma (HCC) is a highly prevalent malignancy that develops in patients with chronic liver diseases and dysregulated systemic and hepatic immunity. The tumor microenvironment (TME) contains tumor-associated macrophages (TAM), cancer-associated fibroblasts (CAF), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) and is central to mediating immune evasion and resistance to therapy. The interplay between these cells types often leads to insufficient antigen presentation, preventing effective anti-tumor immune responses. In situ vaccines harness the tumor as the source of antigens and implement sequential immunomodulation to generate systemic and lasting antitumor immunity. Thus, in situ vaccines hold the promise to induce a switch from an immunosuppressive environment where HCC cells evade antigen presentation and suppress T cell responses towards an immunostimulatory environment enriched for activated cytotoxic cells. Pivotal steps of in situ vaccination include the induction of immunogenic cell death of tumor cells, a recruitment of antigen-presenting cells with a focus on dendritic cells, their loading and maturation and a subsequent cross-priming of CD8+ T cells to ensure cytotoxic activity against tumor cells. Several in situ vaccine approaches have been suggested, with vaccine regimens including oncolytic viruses, Flt3L, GM-CSF and TLR agonists. Moreover, combinations with checkpoint inhibitors have been suggested in HCC and other tumor entities. This review will give an overview of various in situ vaccine strategies for HCC, highlighting the potentials and pitfalls of in situ vaccines to treat liver cancer.

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Targeting Tumor‐Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies

Cited by 30 publications

References 94 publications

LRP1B mutation: a novel independent prognostic factor and a predictive tumor mutation burden in hepatocellular carcinoma

LRP1B mutation: a novel independent prognostic factor and a predictive tumor mutation burden in hepatocellular carcinoma

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

In Situ Vaccination as a Strategy to Modulate the Immune Microenvironment of Hepatocellular Carcinoma

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