Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG
Menée notamment à l'aide d'un modèle murin de cancer mammaire, cette étude met en évidence un mécanisme par lequel des lymphocytes B, ayant migré dans les ganglions lymphatiques après interaction avec les cellules tumorales, favorisent le développement de métastases ganglionnaires en sécrétant des immunoglobulines IgG pathogènes dirigées contre la protéine membranaire glycosylée HSPA4
Primary tumors may create the premetastatic niche in secondary organs for subsequent metastasis. Humoral immunity contributes to the progression of certain cancers, but the roles of B cells and their derived antibodies in premetastatic niche formation are poorly defined. Using a mouse model of spontaneous lymph node metastasis of breast cancer, we show that primary tumors induced B cell accumulation in draining lymph nodes. These B cells selectively promoted lymph node metastasis by producing pathogenic IgG that targeted glycosylated membrane protein HSPA4, and activated the HSPA4-binding protein ITGB5 and the downstream Src/NF-κB pathway in tumor cells for CXCR4/SDF1α-axis-mediated metastasis. High serum anti-HSPA4 IgG was correlated with high tumor HSPA4 expression and poor prognosis of breast cancer subjects. Our findings identify a key role for tumor-educated B cells and their derived antibodies in lymph node premetastatic niche formation, providing potential targets for cancer intervention.