Year: 2025
Type: editorial
Abstract: Second Military Medical University, Shanghai 200433 , P. R. China 6 Shanghai Key Laboratory of Cell Engineering Second Military Medical University, Shanghai 200433 , P. R. China * Corresponding Author: Prof. Zhiying He Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, underscoring the urgent need for improved diagnosis and treatment. One of the most critical aspect for the complexity of the HCC is its tumor microenveronment (TME), a complex structure composed of various immune cells, cancer-associated fibroblasts, endothelial cells, and other tissue-resident cells., The TME plays a crucial role in the occurrence, development, invasion, infiltration, metastasis, spread, and growth of tumors. Understanding the complex interactions between tumor cells and the TME is not only a prerequisite for the rational development of effective anti-tumor therapies but also key to targeted therapy and effective drug delivery. This Research Topic of Frontiers in Immunology explores the latest advances in developing cell or immunotherapies with stable quality and significant efficacy in the context of tumor and immune microenvironment. These innovations offer promising strategies for treating liver tumors that are currently untreatable in clinical practice and provide useful research and translational directions for cell therapy against other solid tumors.Immunotherapy for liver cancer can be broadly categorized into traditional targeted therapy and novel immune cell therapy. Regarding traditional treatments, Zhitao Dong et al. conducted a retrospective real-world study on the poor prognosis and ineffectiveness of existing treatments for advanced intrahepatic cholangiocarcinoma (ICC). Analysis of data from 95 ICC patients revealed that chemotherapy combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors was significantly effective and well-tolerated, representing a potentially better treatment option for advanced unresectable intrahepatic cholangiocarcinoma.However, this conclusion still requires validation through larger-scale prospective cohort studies. Yue Chen et al. also conducted a systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without PD-1 inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). And their result conlcuded that the TLP group had better efficacy for uHCC than that of the TL group, with an acceptable safety profile.Beyond classic sites like PD-1, many studies have focused on novel targets. Haoran Chen et al.elucidated the crucial role of caspase-8 in the development, progression, and drug resistance of HCC, and explored the prospects of targeting caspase-8 as a treatment for HCC. However, the authors also noted that the regulatory role of caspase-8 in the complex TME of HCC is not fully understood. Furthermore, the clinical translation of this approach faces significant technical hurdles, including the lack of highly specific and selective caspase-8 activators and inhibitors, as well as the lack of effective delivery to tumor tissues and the ability to Of course, any immunotherapy, while establishing the effectiveness of drugs and cells, must also acknowledge the unique immune microenvironment of the liver. The liver's immune microenvironment not only inhibits the efficacy of immunotherapeutic drugs but also creates a barrier, leading to drug resistance and reducing the overall effectiveness of treatment. Yanju Liu et al. summarized recent research progress on the immune profile of liver cancer, pointing out that future treatment strategies include combining immunotherapy with other therapies, utilizing targeted therapies to modulate the immune microenvironment, and developing novel drugs that can bypass or counteract liver inhibitory mechanisms, thereby improving the treatment outcomes of liver cancer.In addition to focusing on the progress of immunotherapy for HCC, this Research Topic also summarizes models for liver cancer research and prognostic assessment. Jinjia Song et al. summarized the current research and treatment progress for fibrolamellar carcinoma (FLC), a rare tumor. They particularly elucidated the crucial role of the interaction between FLC epithelial cells, endothelial progenitor cells, stellate cells, and the host's immune microenvironment in the construction of FLC organoids. The review emphasized the key role of the interaction between tumor cells and multiple cell types within the TME in tumor organoid construction, and the concepts mentioned in this review also apply to the construction of organoids for HCC and cholangiocarcinoma.Lastly, as a direct manifestation of the role of the tumor immune microenvironment in tumor recurrence and metastasis, microvascular invasion (MVI) is an independent risk factor for recurrence and metastasis of HCC, highly associated with poor prognosis. Xiaolan Mu et al. identified characteristic genes of MVI and constructed a novel prognostic prediction model for HCC using spatial transcriptome sequencing. This model suggests an increased proportion of macrophages in high-risk patients, indicating that HCC tumor cells may promote HCC metastasis through macrophage cell interactions via activating "migration inhibitory factor (MIF)-CD74" signaling.This study not only provides an assessment model for the prognosis of patients with HCC but also has important clinical significance in differentiating patient types and selecting appropriate treatment options.In summary, this Research Topic provides a systematic and comprehensive overview of the current progress, breakthroughs, existing problems, and solutions in traditional drug immunotherapy and cell therapy for HCC. It underscores the development of sequencing for targeted therapy and cell therapy, as well as combined systemic therapies, for solid tumors such as HCC.WZ drafted the first version. ZH, Y-RL, YW, and XW edited it. All the authors approved the submission.
Source: Frontiers in Immunology
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4417311069
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