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01.06.2010 | Brief Report

Density of tumour stroma is correlated to outcome after adoptive transfer of CD4⁺ and CD8⁺ T cells in a murine mammary carcinoma model

verfasst von: Michele L. Martin, Erika M. Wall, Emily Sandwith, Adam Girardin, Katy Milne, Peter H. Watson, Brad H. Nelson

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2010

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Abstract

Adoptive immunotherapy shows promise for the treatment of cancer; however, partial or mixed responses remain common outcomes due to the heterogeneity of tumours. We studied three murine mammary tumour lines that express an ovalbumin-tagged version of HER-2/neu and reproducibly undergo complete regression (CR), partial regression (PR), or progressive disease (PD) after adoptive transfer of ovalbumin-specific CD8⁺ (OT-I) and CD4⁺ (OT-II) T cells. The three tumour lines were implanted in immunocompetent C57Bl/6 host mice, and established tumours were treated by adoptive transfer of naive OT-I and OT-II T cells. Tumours of the CR and PR classes triggered almost indistinguishable T cell responses in terms of activation, proliferation, trafficking to the tumour site, infiltration of tumour stroma, and intratumoural T cell proliferation; however, tumours of the PR class showed reduced infiltration of tumour epithelium by donor T cells. PD responses were associated with early impairment of T cell activation and proliferation in draining lymph node, followed by negligible infiltration of tumour tissue by donor T cells. Histopathological determinants of outcome were investigated through an unsupervised analysis of 64 untreated tumours representing the three response classes. Tumours of the CR class had proportionately more stroma, which had a looser, more collagen-rich histological appearance. Thus, the amount and composition of tumour stroma distinguished successfully (CR) from unsuccessful (PR or PD) outcomes after adoptive T cell transfer, a finding that might facilitate the design of immunotherapy trials for human breast cancer.

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Titel: Density of tumour stroma is correlated to outcome after adoptive transfer of CD4+ and CD8+ T cells in a murine mammary carcinoma model
verfasst von: Michele L. Martin
Erika M. Wall
Emily Sandwith
Adam Girardin
Katy Milne
Peter H. Watson
Brad H. Nelson
Publikationsdatum: 01.06.2010
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2010
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0559-y

Springer Medizin

Density of tumour stroma is correlated to outcome after adoptive transfer of CD4⁺ and CD8⁺ T cells in a murine mammary carcinoma model

Abstract

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Springer Medizin

Abstract

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