title: Development of metastatic HER2(+) breast cancer is independent of the adaptive immune system.
abstract: The tumour-modulating effects of the endogenous adaptive immune system are rather paradoxical. Whereas some clinical and experimental observations offer compelling evidence for the existence of immunosurveillance, other studies have revealed promoting effects of the adaptive immune system on primary cancer development and metastatic disease. We examined the functional significance of the adaptive immune system as a regulator of spontaneous HER2(+) breast tumourigenesis and pulmonary metastasis formation, using the MMTV-NeuT mouse model in which mammary carcinogenesis is induced by transgenic expression of the activated HER2/neu oncogene. Although T and B lymphocytes infiltrate human and experimental HER2(+) breast tumours, genetic elimination of the adaptive immune system does not affect development of premalignant hyperplasias or primary breast cancers. In addition, we demonstrate that pulmonary metastasis formation in MMTV-NeuT mice is not dependent on the adaptive immune system. Thus, our findings reveal that spontaneous HER2-driven mammary tumourigenesis and metastasis formation are neither suppressed, nor altered by immunosurveillance mechanisms, nor promoted by the adaptive immune system.
authors.affiliation: Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Metamia
authors.initials: M
authors.lastname: Ciampricotti
authors.forename: Kim
authors.initials: K
authors.lastname: Vrijland
authors.forename: Cheei-Sing
authors.initials: CS
authors.lastname: Hau
authors.forename: Tea
authors.initials: T
authors.lastname: Pemovska
authors.forename: Chris W
authors.initials: CW
authors.lastname: Doornebal
authors.forename: Ewoud N
authors.initials: EN
authors.lastname: Speksnijder
authors.forename: Katharina
authors.initials: K
authors.lastname: Wartha
authors.forename: Jos
authors.initials: J
authors.lastname: Jonkers
authors.forename: Karin E
authors.initials: KE
authors.lastname: de Visser
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary*; D016131:Lymphocyte Subsets / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse