探索MFAP2 +癌相关成纤维细胞（CAFs）浸润在胃癌（GC）临床结果和辅助化疗或免疫疗法反应中的预测价值。本研究分别包括几个独立队列，以解剖MFAP2 + CAFs浸润与临床结果、治疗反应和肿瘤微环境的关系。进行药物敏感性分析以预测MFAP2 + CAFs浸润和靶向药物反应之间的关系。采用Kaplan-Meier曲线和log-rank检验比较不同MFAP2 + CAFs浸润患者的临床结果。GC中高MFAP2 + CAFs浸润与整体生存率、无进展生存率和无复发生存率的不良预后相关。MFAP2 + CAFs低浸润的患者更容易从辅助治疗中获益。此外，MFAP2 + CAFs低浸润可预测胃癌患者对免疫疗法的良好反应。具有免疫抑制特征的MFAP2 + CAFs与CD8 + T细胞功能障碍所表征的免疫逃避背景密切相关。我们发现，MFAP2 + CAFs通过释放巨噬细胞迁移抑制因子（MIF）与T细胞、B细胞和巨噬细胞相互作用，进一步提示MFAP2 + CAFs可能通过调节T细胞功能和M2巨噬细胞极化来促进治疗抵抗。免疫抑制性的MFAP2 + CAFs构建了一个免疫逃避的肿瘤微环境，其特征是免疫效应细胞的能力下降，从而在GC患者中预测了不良的临床结果和对辅助治疗和免疫疗法的反应。MFAP2 + CAFs作为GC的治疗靶点的潜力值得深入探索。©2023. Springer Nature Switzerland AG.

To explore the predictive merit of MFAP2+ cancer associated fibroblasts (CAFs) infiltration for clinical outcomes and adjuvant chemotherapy or immunotherapy responsiveness in gastric cancer (GC).In this study, several independent cohorts were included respectively to dissect the relationship of clinical outcomes, therapeutic responses and tumor microenvironment with different MFAP2+ CAFs infiltration. Drug sensitivity analysis was conducted to predict the relationship between MFAP2+ CAFs infiltration and targeted drug response. Kaplan-Meier curves and the log-rank test were used to compare clinical outcomes of patients with different MFAP2+ CAFs infiltration.High MFAP2+ CAFs infiltration yielded inferior prognosis in terms of overall survival, progress free survival and recurrence free survival in GC. Patients with low MFAP2+ CAFs infiltration were more likely to gain benefit from adjuvant therapy. Moreover, low MFAP2+ CAFs infiltration could predict a promising response to immunotherapy in GC patients. MFAP2+ CAFs with immunosuppressive features were highly relevant to immune evasive contexture characterized by the dysfunction of CD8+ T cells. We found that MFAP2+ CAFs communicated with T cells, B cells and Macrophages through releasing macrophage migration inhibitor factor (MIF), which further suggested that MFAP2+ CAFs might promote therapeutic resistance through regulating T cells dysfunction and M2 macrophages polarization.Immunosuppressive MFAP2+ CAFs constructed an immune evasive tumor microenvironment characterized by incapacitated immune effector cells, consequently predicting inferior clinical outcomes and response on adjuvant therapy and immunotherapy in patients with GC. The potential of immunosuppressive MFAP2+ CAFs as a therapeutic target for GC deserved thoroughly exploration.© 2023. Springer Nature Switzerland AG.