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

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

doi:10.2174/0113892010319495241218114812

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

Curr Pharm Biotechnol. 2025 Jan 3. doi: 10.2174/0113892010319495241218114812. Online ahead of print.

Authors

Qing Liu^{1

2

3}, Zu-Chian Chiang^{4

5}, Xiangqian Zhao⁴, Dongya Cui⁴, Xinxin Li², Hao Chen^{1

3}, Fangyu Lin^{1

3}, Tao Jiang^{1

3}, Qi Chen⁴, Xiaoyan Lin^{1

3}, Jizhen Lin^{2

6}

Affiliations

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

PMID: 39773053
DOI: 10.2174/0113892010319495241218114812

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.

Keywords: Immune checkpoint inhibitor; PD-1 mAb; suppressing neovascularization.; thalidomide.