Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG

Gu, Y; Liu, YF; Fu, L; Zhai, LL; Zhu, J; Han, YM; Jiang, YM; Zhang, Y; Zhang, P; Jiang, ZP; Zhang, X; Cao, XT

Cao, XT (reprint author), Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai, Peoples R China.; Cao, XT (reprint author), Second Mil Med Univ, Inst Immunol, Shanghai, Peoples R China.; Cao, XT (reprint author), Chinese Acad Med Sci, Peking Union Med

NATURE MEDICINE, 2019; 25 (2): 312

Abstract

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-kappa B pathway in tumor cells for CXCR4/SDF1 alpha-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.

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