Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase

Cancers frequently evade cytotoxic T lymphocyte-mediated destruction through loss or down-regulation of tumor antigens and antigen-presenting major histocompatibility complex molecules. Therefore, we have concentrated our efforts on immunological strategies that destroy nonmalignant stromal cells es...

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Published inThe Journal of experimental medicine Vol. 207; no. 11; pp. 2469 - 2477
Main Authors Schietinger, Andrea, Philip, Mary, Liu, Rebecca B, Schreiber, Karin, Schreiber, Hans
Format Journal Article
LanguageEnglish
Published United States The Rockefeller University Press 25.10.2010
Subjects
Animals
Bystander Effect - immunology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Fibrosarcoma - immunology
Fibrosarcoma - pathology
Fibrosarcoma - therapy
Immunotherapy
Mice
Mice, Knockout
Neoplasms, Experimental - immunology
Neoplasms, Experimental - pathology
Neoplasms, Experimental - therapy
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Summary:Cancers frequently evade cytotoxic T lymphocyte-mediated destruction through loss or down-regulation of tumor antigens and antigen-presenting major histocompatibility complex molecules. Therefore, we have concentrated our efforts on immunological strategies that destroy nonmalignant stromal cells essential for the survival and growth of cancer cells. In this study, we developed a non-T cell receptor transgenic, immunocompetent tumor model to determine whether tumor-bearing hosts' own immune systems could eliminate cancer cells through stromal targeting and what role CD4(+) T cells play alongside CD8(+) T cells in this process. We found that aggressive cancers could be eradicated by T cell targeting of tumor stroma. However, successful elimination required the cooperation of CD4(+) and CD8(+) T cells not only during the induction phase but also during the effector phase in the tumor microenvironment, implying a new role for CD4(+) T cells that has not been previously described. Our study demonstrates the potential of stromal targeting as a cancer immunotherapy and suggests that successful anticancer strategies must facilitate cooperation between CD4(+) and CD8(+) T cells at the right times and the right places.
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A. Schietinger’s present address is Dept. of Immunology, University of Washington, Seatle, WA.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20092450