Transferable anticancer innate immunity in spontaneous regression/complete resistance mice.

Full Abstract

Spontaneous regression/complete resistance (SR/CR) mice resist very high doses of cancer cells that are lethal to WT mice even at low doses. In this study, we show that this resistance is mediated by rapid infiltration of leukocytes, mostly of innate immunity, in both primary and repeated challenges. Formation of rosettes with infiltrating natural killer cells, neutrophils, and macrophages was required for the subsequent destruction of cancer cells through rapid cytolysis. Highly purified natural killer cells, macrophages, and neutrophils from the SR/CR mice independently killed cancer cells in vitro. The independent killing activity by each subset of effector cells is consistent with the observation that the resistance was abolished by depleting total infiltrating leukocytes but not by depleting only one or two subsets of leukocytes. The resistance was completely transferable to WT recipient mice through SR/CR splenocytes, bone marrow cells, or enriched peritoneal macrophages, either for prevention against subsequent cancer challenges or eradication of established malignancy at distant sites.

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Author information

Author/s: Hicks, Amy M (AM); Riedlinger, Gregory (G); Willingham, Mark C (MC); Alexander-Miller, Martha A (MA); Von Kap-Herr, C (C); Pettenati, Mark J (MJ); Sanders, Anne M (AM); Weir, Holly M (HM); Du, Wei (W); Kim, Joseph (J); Simpson, Andrew J G (AJ); Old, Lloyd J (LJ); Cui, Zheng (Z);

Affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Grants: CA79448 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2006-May; vol 103 (issue 20) : pp 7753-8

Dates: Created 2006/05/17; Completed 2006/07/28; Revised 2008/11/21;

PMID: 16682640, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Cell Line
Cytotoxicity, Immunologic
Homeodomain Proteins - genetics; metabolism
Immunity, Innate - physiology
Leukocytes - immunology; ultrastructure
Lymphocyte Subsets

Mice
Mice, Inbred BALB C
Mice, Inbred Strains
Mice, Knockout
Mice, Nude
Neoplasms, Experimental - immunology; pathology
Phenotype

Associated Chemicals: Homeodomain Proteins (0) ; RAG-1 protein (128559-51-3)

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