This article reports on a novel immunotherapy strategy for gastric and other gastrointestinal cancers using TFF2-MSA, a CXCR4 partial agonist peptide, in combination with anti-PD-1 treatment. Researchers demonstrate that TFF2-MSA synergistically enhances anti-PD-1 efficacy by selectively reducing immunosuppressive neutrophils (PMN-MDSCs), particularly the CXCR4-highly-expressing Hdc-GFP+ subset, in the tumor microenvironment and circulation. Mechanistically, TFF2-MSA acts systemically to suppress cancer-driven granulopoiesis in the bone marrow, contrasting with traditional CXCR4 antagonists which can exacerbate immature myeloid cell mobilization. The resulting immune landscape shows a robust activation of anti-tumoral CD8+ T cells, leading to significant tumor growth inhibition and increased survival in mouse models. Clinical relevance is supported by the finding that low TFF2 levels correlate with elevated PMN-MDSCs and poor prognosis in human gastric cancer patients.

References:

• Qian J, Ma C, Waterbury Q T, et al. A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis[J]. Cancer Cell, 2025.