Strengthening Effect of Thalidomide Combined with an Anti-PD1 Antibody on Enhancing Immunity for Lung Cancer Therapy.

IF 2.2 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current pharmaceutical biotechnology Pub Date : 2025-01-03 DOI:10.2174/0113892010319495241218114812

Qing Liu, Zu-Chian Chiang, Xiangqian Zhao, Dongya Cui, Xinxin Li, Hao Chen, Fangyu Lin, Tao Jiang, Qi Chen, Xiaoyan Lin, Jizhen Lin

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Abstract

Objective: Combining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis.

Methods: We investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis.

Results: THD exhibited regulatory effects on PD-1 in CD4+ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4+ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4+ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8+ T cell infiltration in tumors, and reduced CD34+ intratumoral microvessel density.

Conclusion: This study highlights THD's role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.

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沙利度胺联合抗pd1抗体在肺癌治疗中的增强免疫作用。

目的：结合免疫检查点抑制剂和抗血管生成药物，为对抗免疫检查点和瘤内血管生成共同促进实体瘤生长提供了一种有前景的策略。方法：研究沙利度胺（THD）和抗PD-1抗体（PD-1 mAb）在抑制肿瘤生长、增强免疫和抑制血管生成方面的潜力。结果：THD对CD4+ T细胞的PD-1和癌细胞的PD-L1有调节作用，并对A549和Lewis肺癌（LLC）细胞系的肿瘤生长有抑制作用。与PD-1单抗联合，THD可提高CD4+ T细胞内IL-2和IFN-γ的表达，增强外周血单核细胞（PBMCs）颗粒酶（Gzm-B）的表达，降低CD4+ T细胞内TNF-α的表达。在C57BL/6小鼠中，THD + PD-1 mAb可降低clc源性肺肿瘤的重量和体积，促进肿瘤中CD8+ T细胞的浸润，降低肿瘤内CD34+微血管密度。结论：本研究突出了THD通过改变肿瘤微环境增强PD-1 mAb疗效的作用，为改善PD-1 mAb治疗效果提供了一种临床可行的途径。

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来源期刊

Current pharmaceutical biotechnology 医学-生化与分子生物学

CiteScore

5.60

自引率

3.60%

发文量

203

审稿时长

6 months

期刊介绍： Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.