Immune Checkpoint Inhibitors in Combinations for Hepatocellular Carcinoma

Kalasekar, Sharanya Maanasi; Evason, Kimberley

doi:10.1002/hep.31706

Cited by 16 publications

(19 citation statements)

References 8 publications

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“…Recently, the synergistic effect of systemic therapy and ICBs has been actively reported. VEGF/VEGFR signaling is associated with the immunosuppressive tumor microenvironment, in addition to its primary role in angiogenesis [ 39 ]. For example, VEGF/VEGFR signaling can suppress the function and differentiation of DCs, induce MDSCs [ 40 ].…”

Section: Evidence Of Current Icbs For Hccmentioning

confidence: 99%

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

Han

Yoon

2021

Pharmaceutics

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Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.

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Section: Evidence Of Current Icbs For Hccmentioning

confidence: 99%

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

Han

Yoon

2021

Pharmaceutics

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“…3 Immunotherapy based on immune checkpoints has also been recently used in HCC. 5 However, its efficiency is limited to less than 20%. Therefore, there is a desperate and urgent need for comprehensive research on the mechanisms of development, progression, recurrence, metastasis, and resistance of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have suggested that immunotherapy based on immune checkpoint inhibitors is a promising therapeutic strategy for patients with advanced HCC, while its efficiency remains less than 20%. 5 Therefore, advances in the treatment of HCC are urgently needed, which requires comprehensive investigation on the pathogenesis of HCC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma

Dai¹,

Li²,

Ye³

et al. 2021

J Clin Transl Hepatol

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Background and Aims:Numerous studies have explored the important role of N6-methyladenosine (m 6 A) in cancer. Nonetheless, the interaction between m 6 A and long noncoding RNAs (lncRNAs) is poorly investigated. Herein, we systematically analyzed the role and prognostic value of m 6 A-related lncRNAs in hepatocellular carcinoma (HCC). Methods: The m 6 A-related lncRNAs were identified based on the correlation coefficients with m 6 A-related genes in HCC from The Cancer Genome Atlas. Subsequently, a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate Cox analyses were used to identify independent prognostic factors for overall survival (OS) of HCC; thereafter, a prognostic nomogram was constructed. Results: A total of 259 lncRNAs showed significant correlations with m 6 A in HCC, while 29 lncRNAs had prognostic significance. Further, six critical m 6 A-related lncRNAs (NRAV, SNHG3, KDM4A-AS1, AC074117.1, AC025176.1, and AL031985.3) were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups. Survival analyses revealed that patients in the high-risk group exhibited worse OS, both in the training and validation groups. The risk score was also identified as an independent prognostic factor of OS, and a nomogram was established and verified with superior prediction capacity. Besides, the risk score significantly correlated with the expression of immune checkpoint genes and immune subtypes. Conclusions: These findings indicated the significant role of m 6 A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.

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“…To verify the effects of TB/PTX@RTK-mediated chemo-PDT on the maturation of DCs, we extracted bone marrow cells from the femoral bone marrow of C57BL/6 mice according to previous method and used GM-CSF and IL-4 to differentiate and cultured them into immature bone marrow DCs (BMDCs) [4,10].…”

Section: Bmdc and Bmdc Maturation Assays In Vitromentioning

confidence: 99%

“…ICB therapies, especially programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) monoclonal antibodies (anti-PD-1/PD-L1), could relieve the immune restriction and restore T lymphocyte function in the tumor microenvironment (TME) [7,8]. Multiple types of anti-PD-1/PD-L1 monoclonal antibodies were recently approved by the FDA for the treatment of several types of malignancy, including rst-line therapy for advanced HCC [9,10]. However, the objective remission rate of ICB therapy in these patients was less than 20% [7,11,12], putatively because of the lack of su cient release of tumor-associated antigen (TAA) and in ltration of cytotoxic T lymphocytes (CTLs) [13].…”

Section: Introductionmentioning

confidence: 99%

Chemo-Photodynamic Therapy With Light-Triggered Disassembly of Theranostic Nanoplatform In Combination With Checkpoint Blockade For Immunotherapy of Hepatocellular Carcinoma

Zheng

Chen

et al. 2021

Preprint

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Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods: A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micells were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micells. The targeted fluorescence imaging of TB/PTX@RTK micells and the synergistic antitumor efficacy of TB/PTX@RTK micells-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo.Results: The TB/PTX@RTK micells could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIEgens photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis.Conclusion: Our results suggest that the combination of TB/PTX@RTK micell-mediated chemo-PDT therapy with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic antitumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC.

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Immune Checkpoint Inhibitors in Combinations for Hepatocellular Carcinoma

Cited by 16 publications

References 8 publications

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma

Chemo-Photodynamic Therapy With Light-Triggered Disassembly of Theranostic Nanoplatform In Combination With Checkpoint Blockade For Immunotherapy of Hepatocellular Carcinoma

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