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

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.

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

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.

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.