Lenvatinib Enhances T Cell Immunity and the Efficacy of Adoptive Chimeric Antigen Receptor-Modified T Cells by Decreasing Myeloid-Derived Suppressor Cells  in Cancer

Lu, Mengmeng; Zhang, Xiaokang; Gao, Xiaoge; Sun, Shishuo; Wei, Xiaohuan; Hu, Xiaolei; Huang, Chao; Wang, Bixi; Zhang, Wei; Xu, Heng; Li, Zhen; Feng, Xiaogang; Zheng, Junnian; Zhang, Qing

doi:10.2139/ssrn.3779886

Cited by 1 publication

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“…In a mouse model of HCC, the immunomodulatory activity of lenvatinib led to an enhanced response to anti-PD-1 treatment. In 2021, it was also suggested in a small retrospective study in which patients with HCC received lenvatinib with pembrolizumab or nivolumab (56,57).…”

Section: Tumor Microenvironment and The Response To Systemic Treatmentmentioning

confidence: 99%

The immune landscape of hepatocellular carcinoma‑where we are? (Review)

et al. 2022

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Hepatocellular carcinoma (HCC) is one of the most common types of cancer diagnosed worldwide. After a decade of stagnation, several novel compounds have recently been shown to be effective in the treatment of HCC. Since immunotherapy is associated with important clinical benefits in some, but not all patients, it is essential to identify reliable predictive biomarkers. As the complex interplay between hepatocytes and immune cells is highly dependent on the tumor microenvironment, the tumor microenviroment has been suggested to be an important factor associated with the response to therapy and is currently being extensively investigated. Within this network, several important factors should be highlighted. Most of the cells are hepatocytes, but fibroblasts, endothelial cells, and immune cells are also present. Tumor-infiltrating leukocytes include several populations of cells and each of them plays a role in forming the tumor environment. Some of these cells may have antitumor effects, whereas others may be associated with the progression of the disease. The most important subsets include tumor-associated macrophages, tumor-associated neutrophils, and lymphocytes. These groups are described in the present review. The immune response is controlled by immune checkpoint molecules. One of the most important molecules involved in this checkpoint process seems to be the programmed death-1 (PD-1) receptor, which typically is induced on activated T cells, natural killer (NK) cells, B cells, and antigen-presenting cells. On the other hand, programmed death ligand 1 (PD-L1) is expressed by tumor cells, hepatocytes and hepatic stellate cells, and Kupffer cells or liver sinusoidal cells. Complex interactions between ligands and receptors are dependent on the signals from the microenvironment leading to either cancer development or apoptosis. Evidence from several studies indicates that patients with higher expression levels of PD-L1 on tumor cells or immune cells are more likely to achieve beneficial results from treatment with checkpoint blockers. This review focuses on the basic information regarding the microenvironment and its components, particularly on immune system involvement. Contents 1. Introduction 2. Myeloid-derived suppressor cells (MDSCs) 3. Tumor-associated macrophages (TAMs) 4. Tumor-infiltrating leukocytes (TILs) 5. Tumor-associated neutrophils (TANs) 6. Tumor microenvironment and response to systemic treatment 7. Immune checkpoint inhibition 8. Immune checkpoint inhibitors assessed for treatment of HCC 9. Immune microenvironment factors associated with the response to immunotherapy 10. Additional potential biomarkers and predictive factors for the response to immunotherapy 11. Conclusions

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Section: Tumor Microenvironment and The Response To Systemic Treatmentmentioning

confidence: 99%