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

Qing Liu ¹Zu-Chian Chiang ²Xiangqian Zhao ³Dongya Cui ³Xinxin Li ⁴Hao Chen ⁵Fangyu Lin ⁵Tao Jiang ⁵Qi Chen ³Xiaoyan Lin ⁵Jizhen Lin⁶

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作者信息

1. The Oncology Department of Union Hospital, Fujian Medical University, Fuzhou, Fujian, China||The Cancer Center, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China||Fujian Provincial Key Laboratory of Translational Cancer Medicine, China
2. Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, Fujian, China||College of photonic and electronic engineering, Fujian Normal University, Fuzhou, Fujian, China
3. Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, Fujian, China
4. The Cancer Center, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China
5. The Oncology Department of Union Hospital, Fujian Medical University, Fuzhou, Fujian, China||Fujian Provincial Key Laboratory of Translational Cancer Medicine, China
6. The Cancer Center, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China||The Department of Otolaryngology, Head & Neck Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
折叠

Abstract

Objectives: 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-a 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.

Key words

Immune checkpoint inhibitor/PD-1 mAb/thalidomide/suppressing neovascularization/peripheral blood mononuclear cells/tumors

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出版年

2025

Current pharmaceutical biotechnology

SCI

ISSN：1389-2010

参考文献量75

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