Development of metastatic HER2+ breast cancer is independent of the adaptive immune system

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...

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Vydáno v:The Journal of pathology Ročník 224; číslo 1; s. 56 - 66
Hlavní autoři: Ciampricotti, Metamia, Vrijland, Kim, Hau, Cheei-Sing, Pemovska, Tea, Doornebal, Chris W, Speksnijder, Ewoud N, Wartha, Katharina, Jonkers, Jos, de Visser, Karin E
Médium: Journal Article
Jazyk:angličtina
Vydáno: Chichester, UK John Wiley & Sons, Ltd 01.05.2011
Wiley
Témata:
adaptive immune system
Adaptive Immunity - immunology
Animal models
Animals
Biological and medical sciences
Breast cancer
Carcinogenesis
Cell Transformation, Neoplastic - immunology
ErbB-2 protein
Female
Gynecology. Andrology. Obstetrics
Her2/neu
Humans
Hyperplasia
Immune system
Immune Tolerance - immunology
Immunologic Surveillance - immunology
Immunosurveillance
innate immune system
Investigative techniques, diagnostic techniques (general aspects)
Lung
Lung Neoplasms - immunology
Lung Neoplasms - secondary
Lymphocyte Subsets - immunology
Lymphocytes B
Mammary gland diseases
Mammary Neoplasms, Experimental - immunology
Mammary Neoplasms, Experimental - metabolism
Medical sciences
Metastases
metastasis
Mice
Mice, Transgenic
Neoplasm Transplantation
Oncogenes
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Receptor, ErbB-2 - metabolism
Tumor Microenvironment - immunology
Tumorigenesis
Tumors
Breast disease
Her2/neu
erbB2 Gene
Natural immunity
Breast cancer
Malignant tumor
Metastasis
adaptive immune system
immunosurveillance
innate immune system
Mammary gland diseases
Immunological surveillance
Anatomic pathology
Development
Advanced stage
Metastatic
Cancer
Immune system
ISSN:0022-3417, 1096-9896, 1096-9896
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Shrnutí: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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Bibliografie:ArticleID:PATH2837
istex:86CEE8F2F34138D6B121F1B376618F2A5E4B48CF
Supporting Information: Figure S1. Increased infiltration of immune cells in human and mouse HER2+ breast cancer.Supporting Information: Figure S2. Absence of CD4+ and CD8+ T cells and CD20+/CD19+ B cells in NeuT/Rag-2−/− mice.Supporting Information: Figure S3. The adaptive immune system does not modulate proliferation of breast cancer cells in MMTV-NeuT mice.Supporting Information: Figure S4. Influx of Gr1+ CD11b+ granulocytes in the tumour microenvironment and spleen is not altered by the absence of the adaptive immune system.Supporting Information: Figure S5. Size-categories of pulmonary metastases.Supporting Information: Table S1. Detailed information about antibodies used for (a) immunohistochemistry and (b) flow cytometry.Supporting Information: Legends to Figure S1 to S5
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ISSN:0022-3417
1096-9896
1096-9896
DOI:10.1002/path.2837