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01-11-2009 | Original Article

Mammary tumors with diverse immunological phenotypes show differing sensitivity to adoptively transferred CD8+ T cells lacking the Cbl-b gene

Authors: Taimei Yang, Michele L. Martin, Julie S. Nielsen, Katy Milne, Erika M. Wall, Wendy Lin, Peter H. Watson, Brad H. Nelson

Published in: Cancer Immunology, Immunotherapy | Issue 11/2009

Abstract

We tested the efficacy of CD8+ T cells lacking the Cbl-b gene against a panel of mammary tumor lines with different intrinsic sensitivities to T cells. Mice bearing established tumors expressing an ovalbumin-tagged version of HER-2/neu underwent adoptive transfer with Cbl-b-replete or -null CD8+ T cells from OT-I T cell receptor transgenic donor mice. In general, Cbl-b-null OT-I cells showed enhanced expansion, persistence, and capacity for tumor infiltration. This resulted in markedly enhanced efficacy against two tumor lines that normally demonstrate complete (NOP21) or partial (NOP23) regression. Moreover, a third tumor line (NOP6) that normally demonstrates progressive disease underwent complete regression in response to Cbl-b-null OT-I cells. However, a fourth tumor line (NOP18) was resistant to Cbl-b-null OT-I cells owing to a profound barrier to lymphocyte infiltration. Thus, Cbl-b-null CD8+ T cells are generally more efficacious but are nonetheless unable to mediate curative responses against all tumor phenotypes.

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Title: Mammary tumors with diverse immunological phenotypes show differing sensitivity to adoptively transferred CD8+ T cells lacking the Cbl-b gene
Authors: Taimei Yang
Michele L. Martin
Julie S. Nielsen
Katy Milne
Erika M. Wall
Wendy Lin
Peter H. Watson
Brad H. Nelson
Publication date: 01-11-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 11/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0698-3

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