T cell homeostatic proliferation elicits effective antitumor autoimmunity

Development of tumor immunotherapies focuses on inducing autoimmune responses against tumor-associated self-antigens primarily encoded by normal, unmutated genes. We hypothesized that such responses could be elicited by T cell homeostatic proliferation in the periphery, involving expansion of T cell...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2002-07, Vol.110 (2), p.185-192
Main Authors: Dummer, Wolfgang, Niethammer, Andreas G, Baccala, Roberto, Lawson, Brian R, Wagner, Norbert, Reisfeld, Ralph A, Theofilopoulos, Argyrios N
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens, Neoplasm
Autoantigens
Autoimmunity
CD8-Positive T-Lymphocytes - immunology
Colonic Neoplasms - immunology
Colonic Neoplasms - therapy
Cytotoxicity, Immunologic
Homeostasis
Immunologic Memory
Immunotherapy
Interferon-gamma - biosynthesis
Lymphocyte Activation
Melanoma, Experimental - immunology
Melanoma, Experimental - therapy
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms, Experimental - immunology
Neoplasms, Experimental - therapy
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Vitiligo - immunology
Vitiligo - pathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Development of tumor immunotherapies focuses on inducing autoimmune responses against tumor-associated self-antigens primarily encoded by normal, unmutated genes. We hypothesized that such responses could be elicited by T cell homeostatic proliferation in the periphery, involving expansion of T cells recognizing self-MHC/peptide ligands. Herein, we demonstrate that sublethally irradiated lymphopenic mice transfused with autologous or syngeneic T cells showed tumor growth inhibition when challenged with melanoma or colon carcinoma cells. Importantly, the antitumor response depended on homeostatic expansion of a polyclonal T cell population within lymph nodes. This response was effective even for established tumors, was characterized by CD8(+) T cell-mediated tumor-specific cytotoxicity and IFN-gamma production, and was associated with long-term memory. The results indicate that concomitant induction of the physiologic processes of homeostatic T cell proliferation and tumor antigen presentation in lymph nodes triggers a beneficial antitumor autoimmune response.
ISSN:0021-9738
DOI:10.1172/JCI0215175