Adverse effects of PD-1 targeted immunotherapy in NAFLD-triggered HCC

Pfister, D; Nunez, N; Sinha, A; Weiner, Assaf; Deckowska, A; Pinter, M; Govaere, Olivier; Müller, F; Anstee, QM; Entgleitner, T; Rad, Roland; Pinyol, Roser; Torrecilla, Sara; Dudek, M; Knolle, P; Weber, Angelika; Lengenhagger, D; Llovet, J.M.; Amit, Ido; Meissner, F; Becher, B; Heikenwälder, M

doi:10.1055/s-0039-3402254

Cited by 2 publications

(4 citation statements)

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“…105 140 MASH has been found to limit the efficiency of immunotherapy. 23 Compared with viral HCC, a reduction of GZMB + CD4 + /CD8 + T cells was observed in MASH-HCC by using spatial proteome analysis, whereas interactions of PD-1 + CD8 + T cells and PD-L1 + ICOS + MDSCs or TAMs were enriched, demonstrating an immunosuppressive microenvironment in MASH-HCC which may impede treatment response. 141 Therefore, understanding the etiology-related TIME in liver cancer may facilitate the development of effective treatment strategies with immunotherapy.…”

Section: Challenges and Opportunitiesmentioning

confidence: 91%

“…The heterogeneity of liver TIME among patients mainly reflects specific enrichment of certain immune cell states or related cellular communications, while the heterogeneity within a patient indicates the diverse functional states of immune cells and their spatial relationships with the tumor. 22 23 24 25 26 In this review, we highlight the heterogeneity of the major immune cells in the liver TIME and provide an update on how the emerging single cell and spatial technologies unveil the heterogeneity and plasticity of each cell type. We also delve into the emergent properties of the cellular networks in regulating immune responses in the context of liver cancer.…”

Section: Lay Summarymentioning

confidence: 99%

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Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives

Li,

Liu,

Lee

et al. 2024

Semin Liver Dis

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Primary liver cancer is a solid malignancy with a high mortality rate. The success of immunotherapy has shown great promise in improving patient care and highlights a crucial need to understand the complexity of the liver tumor immune microenvironment (TIME). Recent advances in single-cell and spatial omics technologies, coupled with the development of systems biology approaches, are rapidly transforming the landscape of tumor immunology. Here we review the cellular landscape of liver TIME from single-cell and spatial perspectives. We also discuss the cellular interaction networks within the tumor cell community in regulating immune responses. We further highlight the challenges and opportunities with implications for biomarker discovery, patient stratification, and combination immunotherapies.

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Section: Challenges and Opportunitiesmentioning

confidence: 91%

Section: Lay Summarymentioning

confidence: 99%

Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives

Li,

Liu,

Lee

et al. 2024

Semin Liver Dis

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“…Strikingly, prophylactic treatment increased HCC incidence, highlighting the important protective mechanisms of inhibitory checkpoints. 160 Even in PD-1 responsive liver cancer mouse models, efficacy was abrogated by diet-induced MASLD/MASH, which was caused by diet-associated impaired CTL metabolism and motility. Remarkably, this effect could be rescued by additional metformin treatment.…”

Section: Mechanisms Of Primary Resistancementioning

confidence: 99%

“…153 Fittingly, subgroup-specific meta-analyses of multiple randomized controlled trials demonstrated a higher survival benefit for patients with viral HCC compared to non-viral etiology. 149 160 However, the matter is more complicated, as patients of non-viral etiology actually seem to benefit from double ICI therapy (anti-PD-L1 plus anti-CTLA-4). 163 Furthermore, it is not clear how many patients with non-viral HCC actually suffer from MASLD.…”

Section: Mechanisms Of Primary Resistancementioning

confidence: 99%

Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?

Werner,

Kuzminskaya,

Lurje

et al. 2024

Semin Liver Dis

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Primary liver cancer, represented mainly by hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (CCA), is one of the most common and deadliest tumors worldwide. While surgical resection or liver transplantation are the best option in early disease stages, these tumors often present in advanced stages and systemic treatment is required to improve survival time. The emergence of immune checkpoint inhibitor therapy has had a positive impact especially on the treatment of advanced cancers, thereby establishing immunotherapy as part of first-line treatment in HCC and CCA. Nevertheless, low response rates reflect on the usually cold or immunosuppressed tumor microenvironment of primary liver cancer. In this review, we aim to summarize mechanisms of resistance leading to tumor immune escape with a special focus on the composition of tumor microenvironment in both HCC and CCA, also reflecting on recent important developments in ICI combination therapy. Furthermore, we discuss how combination of immune checkpoint inhibitors with established primary liver cancer treatments (e.g. multikinase inhibitors and chemotherapy) as well as more complex combinations with state-of-the-art therapeutic concepts may re-shape the tumor microenvironment, leading to higher response rates and long-lasting anti-tumor immunity for primary liver cancer patients.

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Adverse effects of PD-1 targeted immunotherapy in NAFLD-triggered HCC

Cited by 2 publications

References 0 publications

Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives

Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives

Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?

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