Transarterial Embolization Modulates the Immune Response within                     Target and Nontarget Hepatocellular Carcinomas in a Rat Model

Tischfield, David J.; Gurevich, Alexey; Johnson, Omar; Gatmaytan, Isabela; Nadolski, Gregory J.; Soulen, Michael C.; Kaplan, David E.; Furth, Emma E.; Hunt, Stephen; Gade, T.

doi:10.1148/radiol.211028

Cited by 43 publications

(24 citation statements)

References 40 publications

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“… 22 , 28 Thus, it can locoregionally induce immunogenic cell death in HCC and turn the immunosuppressive “cold tumor” into an immunogenic “hot tumor” by restoring the immune microenvironment to further improve immune response. 23 , 35 , 36 Third, there is a close relationship between angiogenesis and suppression of anti-tumor immunity. The VEGF, a key regulator factor of tumor angiogenesis, can directly influence immune cells and facilitate immune evasion, and indirectly influence immunity by increasing vessel permeability.…”

Section: Discussionmentioning

confidence: 99%

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)

Zhu

Huang

et al. 2023

Sig Transduct Target Ther

115

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There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

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Section: Discussionmentioning

confidence: 99%

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)

Zhu

Huang

et al. 2023

Sig Transduct Target Ther

115

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“…It is also important to note that in addition to hyperthermia, transarterial embolization is a cornerstone in the management of HCC. Recent studies, such as those by Tischfield et al 34 , have investigated the immunologic ramifications of this locoregional therapy. In this study, the authors found that embolization performed on autochthonous tumors in a rat HCC model resulted in increased infiltration of lymphocytes as well as PD-L1 expression, a finding consonant with the results of this study.…”

Section: Discussionmentioning

confidence: 99%

Immune modulation by molecularly targeted photothermal ablation in a mouse model of advanced hepatocellular carcinoma and cirrhosis

Muñoz

Dupuis

Williams

et al. 2022

Sci Rep

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Immunotherapy is a promising new treatment approach for hepatocellular carcinoma (HCC), but there are numerous barriers to immunotherapy in HCC, including an immunosuppressive microenvironment and the “immunotolerance” of the liver. Hyperthermia treatment modalities are standard of care for early stage HCC, and hyperthermia is known to have immunomodulatory effects. We have developed a molecularly targeted photothermal ablation (MTPA) technology that provides thermally tunable, tumor-specific heat generation. The purpose of this study was to evaluate the morphologic and immunologic effects of MTPA in an immunotherapy-resistant syngeneic mouse model of HCC in a background of toxin-induced cirrhosis. We found that the anatomic, cellular, and molecular features of this model recapitulate the characteristics of advanced human HCC. MTPA as a monotherapy and in combination with immune checkpoint therapy significantly increased intratumoral CD3+ and activated CD8+ T cells while decreasing regulatory T cells relative to control or immune checkpoint therapy alone based on immunohistochemistry, flow cytometry, and single cell RNA sequencing data. Furthermore, we identified evidence of MTPA’s influence on systemic tumor immunity, with suppression of remote tumor growth following treatment of orthotopic tumors. The results of this study suggest that tumor-specific hyperthermia may help overcome resistance mechanisms to immunotherapy in advanced HCC.

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“…89,90 TACE can be a locoregional inducer of immunogenic cell death in HCC and transform the immunosuppressive 'cold tumour' into a 'hot tumour' by restoring the immune microenvironment. 13,14,83,91 T A B L E 3 Selected randomised controlled trials identifying locoregional therapies combined with systemic agents in HCC.…”

Section: Transarterial Chemoembolization With Immunotherapy-based Reg...mentioning

confidence: 99%

Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives

Chen,

Jin,

Zhong

et al. 2024

UEG Journal

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Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer‐related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real‐world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

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Transarterial Embolization Modulates the Immune Response within Target and Nontarget Hepatocellular Carcinomas in a Rat Model

Cited by 43 publications

References 40 publications

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)

Immune modulation by molecularly targeted photothermal ablation in a mouse model of advanced hepatocellular carcinoma and cirrhosis

Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives

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