Effects of Vinorelbine on M2 Macrophages in Non-Small Cell Lung Cancer

Tumor-associated macrophages (TAMs) significantly influence tumor progression and patient responses to conventional chemotherapy. However, the interplay between anti-cancer drugs, immune responses in the tumor microenvironment, and their implications for cancer treatment remains poorly understood. This study investigates the effects of vinorelbine on M2 macrophages in lung cancer and its capacity to modulate TAMs toward an M1 phenotype. Peripheral blood mononuclear cells (PBMCs) were polarized into M2 macrophages, and subsequent phenotype alterations upon vinorelbine treatment were assessed. Additionally, we evaluated vinorelbine's impact on gene and protein expression associated with cancer progression and cell invasion in non-small-cell lung cancer (NSCLC) cells indirectly co-cultured with M2 macrophages. Notably, vinorelbine, particularly at low concentrations, reprogrammed M2 macrophages to exhibit M1-like characteristics. While M2 macrophages enhanced cancer cell invasion, vinorelbine significantly mitigated this effect. M2 macrophages led to the overexpression of numerous genes linked to tumor growth, angiogenesis, invasion, and immune suppression in NSCLC cells, increasing the BCL2/BAX ratio and promoting cellular resistance to apoptosis. The anti-tumor efficacy of vinorelbine appears to be partly attributed to the reprogramming of M2 macrophages to the M1 phenotype, suggesting that low-dose vinorelbine may optimize therapeutic outcomes while minimizing toxicity in cancer patients.