Journal article
NK depletion results in increased CCL22 secretion and Treg levels in Lewis Lung Carcinoma via the accumulation of CCL22-secreting CD11b(+)CD11c(+) cells
International journal of cancer, Vol.127(11), pp.2598-2611
12/01/2010
DOI: 10.1002/ijc.25281
PMCID: PMC2947555
PMID: 20198623
Abstract
Tumor-induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T-cells (Tregs). Previous studies demonstrated that NK-dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK-derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC-bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK-depleted LLC-bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22-producing cellular fractions in LLC-bearing lungs. A novel CD11b(+)CD11c(+) cell population was identified that accumulates in large numbers in NK-depleted LLC-bearing lung tissue. These CD11b(+)CD11c(+) cells secreted large amounts of CCL22 that may overcompensate for the loss of NK-derived CCL22 in the lungs of NK-depleted LLC-bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC-bearing lungs.
Details
- Title: Subtitle
- NK depletion results in increased CCL22 secretion and Treg levels in Lewis Lung Carcinoma via the accumulation of CCL22-secreting CD11b(+)CD11c(+) cells
- Creators
- Adam W. Mailloux - Medical University of South CarolinaAnna-Maria A. Clark - Ralph H. Johnson VA Medical CenterM. Rita I. Young - Ralph H. Johnson VA Medical Center
- Resource Type
- Journal article
- Publication Details
- International journal of cancer, Vol.127(11), pp.2598-2611
- Publisher
- Wiley
- DOI
- 10.1002/ijc.25281
- PMID
- 20198623
- PMCID
- PMC2947555
- ISSN
- 0020-7136
- eISSN
- 1097-0215
- Number of pages
- 14
- Grant note
- R01CA085266 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA8566; 1R01CA128837; R01DE018168 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Medical Research Service of the Veteran's Affairs R01DE018168 / NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR)
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297425802771
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