Work

Paclitaxel drives TREM2+ macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

Year: 2026

Type: article

Abstract: Paclitaxel and nab-paclitaxel differ in therapeutic efficacy and modulation of the tumor immune microenvironment, yet the molecular basis remains poorly defined. Here, based on a meta-analysis, we first show that treatment with nab-paclitaxel results in a higher overall response rate and pathological complete response compared to paclitaxel in female patients with breast cancer. Notably, TREM2 expression in macrophages is elevated in primary tumors of paclitaxel- but not nab-paclitaxel-treated female patients. In metastatic breast cancer, TREM2+ macrophage infiltration is increased in primary tumors. In breast cancer models in female mice, paclitaxel, but not nab-paclitaxel, promotes lung metastasis by recruiting TREM2+ macrophages to primary tumors. Mechanistically, paclitaxel enhances the ATF3-FGF2 axis in breast cancer cells; secreted FGF2 activates the EGR1-TREM2-EMT cytokine axis in macrophages. Genetic ablation of Trem2 or pharmacologic targeting with antisense oligonucleotides suppress paclitaxel-induced breast cancer lung metastasis in vivo. Collectively, our findings demonstrate that paclitaxel, but not nab-paclitaxel, stimulates TREM2 expression and expands TREM2+ macrophages, suggesting that TREM2 targeting could enhance paclitaxel efficacy while limiting metastasis. Taxanes, including paclitaxel (PTX) and Nab-PTX (comprising PTX bound to albumin nanoparticles), are first-line chemotherapeutic agents in breast cancer therapies. Here, the authors report that PTX, but not Nab-PTX, induces the expansion of tumor-promoting TREM2+ macrophages as a mechanism underlying the inferior antitumor efficacy of PTX compared with Nab-PTX in patients with breast cancer.

Source: Nature Communications

DOI: 10.1038/s41467-026-69060-5