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Oncogene-targeting T cells reject large tumors while oncogene inactivation selects escape variants in mouse models of cancer

Item Type:Article
Title:Oncogene-targeting T cells reject large tumors while oncogene inactivation selects escape variants in mouse models of cancer
Creators Name:Anders, K. and Buschow, C. and Herrmann, A. and Milojkovic, A. and Loddenkemper, C. and Kammertoens, T. and Daniel, P. and Yu, H. and Charo, J. and Blankenstein, T.
Abstract:The genetic instability of cancer cells frequently causes drug resistance. We established mouse cancer models, which allowed targeting of an oncogene by drug-mediated inactivation or monospecific CD8(+) effector T (T(E)) cells. Drug treatment of genetically unstable large tumors was effective but selected resistant clones in the long term. In contrast, T(E) cells completely rejected large tumors (≥500 mm(3)), if the target antigen was cancer-driving and expressed in sufficient amounts. Although drug-mediated oncogene inactivation selectively killed the cancer cells and left the tumor vasculature intact, which likely facilitated survival and growth of resistant clones, T(E) cell treatment led to blood vessel destruction and probably "bystander" elimination of escape variants, which did not require antigen cross-presentation by stromal cells.
Keywords:Animals, Mice
Source:Cancer Cell
ISSN:1535-6108
Publisher:Cell Press (U.S.A.)
Volume:20
Number:6
Page Range:755-767
Date:13 December 2011
Official Publication:https://doi.org/10.1016/j.ccr.2011.10.019
PubMed:View item in PubMed

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