Breast Cancer Research and Treatment

, Volume 121, Issue 3, pp 753–763

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

  • Michele L. Martin
  • Erika M. Wall
  • Emily Sandwith
  • Adam Girardin
  • Katy Milne
  • Peter H. Watson
  • Brad H. Nelson
Brief Report

DOI: 10.1007/s10549-009-0559-y

Cite this article as:
Martin, M.L., Wall, E.M., Sandwith, E. et al. Breast Cancer Res Treat (2010) 121: 753. doi:10.1007/s10549-009-0559-y

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.

Keywords

Adoptive immunotherapy Breast cancer Stroma OT-I OT-II T cell Infiltration 

Supplementary material

10549_2009_559_MOESM1_ESM.pdf (160 kb)
Supplementary material 1 (PDF 161 kb)

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Michele L. Martin
    • 1
    • 2
  • Erika M. Wall
    • 3
  • Emily Sandwith
    • 3
  • Adam Girardin
    • 3
  • Katy Milne
    • 1
  • Peter H. Watson
    • 1
    • 3
    • 4
  • Brad H. Nelson
    • 1
    • 2
    • 3
    • 5
  1. 1.Trev and Joyce Deeley Research CentreBritish Columbia Cancer AgencyVictoriaCanada
  2. 2.Department of BiologyUniversity of VictoriaVictoriaCanada
  3. 3.Department of Biochemistry/MicrobiologyUniversity of VictoriaVictoriaCanada
  4. 4.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  5. 5.Department of Medical GeneticsUniversity of British Columbia2329 West MallVancouverCanada

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