The CD39+ HBV surface protein-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-HCC activity

Zou, Fan; Tan, Jizhou; Liu, Ting; Liu, Bingfeng; Tang, Yaping; Zhang, Hui; Li, Jiaping

doi:10.1016/j.ymthe.2021.01.021

Cited by 41 publications

(45 citation statements)

References 44 publications

(59 reference statements)

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“… 9 Inhibitors targeting immune checkpoints (ICs), such as anti-PD-1/L1 and anti-CTLA-4 monoclonal antibodies (mAbs), have been used to treat non-small cell lung cancer, 10 melanoma, 11 and breast cancer. 12 Tumor-infiltrating lymphocytes (TILs) 13 and macrophages 14 have also been studied in preclinical or clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Wang

Zhang

et al. 2022

Ther Adv Med Oncol

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Tumor-associated macrophages (TAMs), the most abundant inflammatory cell group in the tumor microenvironment, play an essential role in tumor immune regulation. The infiltration degree of TAMs in the tumor microenvironment is closely related to tumor growth and metastasis, and TAMs have become a promising target in tumor immunotherapy. Molecular imaging is a new interdisciplinary subject that combines medical imaging technology with molecular biology, nuclear medicine, radiation medicine, and computer science. The latest progress in molecular imaging allows the biological processes of cells to be visualized in vivo, which makes it possible to better understand the density and distribution of macrophages in the tumor microenvironment. This review mainly discusses the application of targeting TAM in tumor immunotherapy and the imaging characteristics and progress of targeting TAM molecular probes using various imaging techniques.

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Section: Introductionmentioning

confidence: 99%

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Wang

Zhang

et al. 2022

Ther Adv Med Oncol

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“…Preliminary evidence suggests that the anticancer effects of sorafenib in HCC patients are related to these mechanisms. e results of previous studies have confirmed that SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 play important roles in cancer progression [28][29][30][31][32][33][34][35][36][37][38][39]. SLC41A3 is a member of solute carrier family 41 and is involved in many cellular processes.…”

Section: Discussionmentioning

confidence: 77%

A Risk Model Based on Sorafenib-Response Target Genes Predicts the Prognosis of Patients with HCC

Liu

Zeng

et al. 2022

Journal of Oncology

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Sorafenib is used to treat digestive system tumors in patients who do not respond to or cannot tolerate surgery. However, the roles and inhibitory mechanisms of sorafenib against hepatocellular carcinoma (HCC) are unclear. Differentially expressed genes in tissues from responders and nonresponders to sorafenib were investigated using the HCC GSE109211 data set. Biological functions and mechanisms were studied using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The expression levels of differential expressed target genes were identified in HCC tissues, using The Cancer Genome Atlas database, and their prognostic and diagnostic values were explored using survival and receiver operating characteristic curve analysis. A nomogram and risk model of sorafenib-response target genes enabled the evaluation of the prognosis of patients with HCC. The relationship between risk scores and levels of infiltrating immune cells was visualized via correlation analysis. We identified 1620 sorafenib-response target genes involved in the PPAR signaling pathway, antigen processing and presentation, and ferroptosis. SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 were independent risk factors for a poor prognosis for patients with HCC and had diagnostic value. A risk model based on SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 expression showed that patients with HCC in the high-risk group had a worse prognosis. Consensus-clustering analysis (performed with K set to 2) distinguished two clusters (the cluster 1 and cluster 2 groups). Patients in cluster 1 survived significantly longer than those in cluster 2. The risk score correlated with the levels of T cells, cytotoxic lymphocytes, CD8+ T cells, macrophages, memory B cells, follicular helper T cells, and other immune cells. The high risk based on the sorafenib-response targets SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 represented the poor prognosis for patients with HCC and significantly correlated with the levels of immune infiltrating cells in HCC.

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“…According to the authors, CD39 can serve as a biomarker to identify both personalized tumor-reactive CD8+ T cells as well as active CAR-T cells. Besides phenotypic identification, CD39 expression is also necessary for the cytotoxic effect of CD8 CARs and positively regulates antitumor activity ( 73 ). The TRM marker CD103 is a tissue homing molecule important for effector T cell trafficking as well as a promising prognosis biomarker for assessment of tumor-reactive TILS in various types of cancer, such as lung cancer, ovarian cancer and cervical cancers.…”

Section: Challenges and Engineering Strategies To Overcome Car-t Cell...mentioning

confidence: 99%

Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

et al. 2022

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During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encountered by CAR-T cells in solid malignancies is the immunosuppressive tumor microenvironment (TME). The TME impedes tumor trafficking and penetration of T lymphocytes and installs an immunosuppressive milieu by producing suppressive soluble factors and by overexpressing negative immune checkpoints. In order to overcome these hurdles, new CAR-T cells engineering strategies were designed, to potentiate tumor recognition and infiltration and anti-cancer activity in the hostile TME. In this review, we provide an overview of the major mechanisms used by tumor cells to evade immune defenses and we critically expose the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors.

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The CD39+ HBV surface protein-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-HCC activity

Cited by 41 publications

References 44 publications

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

A Risk Model Based on Sorafenib-Response Target Genes Predicts the Prognosis of Patients with HCC

Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

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