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Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice
Susan E Erdman1, Jane J Sohn, Varada P Rao
1Division of Comparative Medicine and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. serdman@mit.edu
Abstract:
Colorectal cancer in humans results from sequential genetic changes in intestinal epithelia commencing with inactivation of the APC tumor suppressor gene. Roles for host immunity in epithelial tumorigenesis are poorly understood. It has been previously shown that CD4+CD25+ lymphocytes inhibit colitis-associated epithelial tumors in Rag-deficient mice. Here we show that addition of CD4+CD25+ lymphocytes in ApcMin/+ mice reduces multiplicity of epithelial adenomas. Interleukin-10 was required in regulatory cells for therapeutic effect. Recipients of regulatory cells showed increased apoptosis and down-regulation of cyclooxygenase-2 within tumors coincident with tumor regression. These data suggest a role for regulatory lymphocytes in epithelial homeostasis in the ApcMin/+ mouse model of intestinal polyposis. Similarities with cancer of the breast, prostate, lung, and other sites raise the possibility of broader roles for regulatory lymphocytes in prevention and treatment of epithelial cancers in humans.
Insights
Regulatory lymphocytes, specifically CD4+CD25+ cells, were found to reduce intestinal adenomas in mice. This therapeutic effect, dependent on Interleukin-10, suggests a role for immune cells in preventing epithelial cancers.
Area of Science:
- Immunology
- Gastroenterology
- Oncology
Background:
- Colorectal cancer arises from genetic alterations in intestinal cells, notably APC gene inactivation.
- The influence of host immunity on epithelial tumor development remains largely unclear.
- Previous studies indicated CD4+CD25+ lymphocytes can inhibit colitis-associated epithelial tumors in specific mouse models.
Purpose of the Study:
- To investigate the impact of CD4+CD25+ lymphocytes on intestinal adenoma formation in ApcMin/+ mice.
- To determine the role of Interleukin-10 in the regulatory function of these lymphocytes.
- To explore the mechanisms underlying tumor regression induced by regulatory cells.
Main Methods:
- Administered CD4+CD25+ lymphocytes to ApcMin/+ mice.
- Utilized Interleukin-10 deficient regulatory cells to assess its necessity.
- Analyzed tumor multiplicity, apoptosis, and cyclooxygenase-2 expression in recipient mice.
Main Results:
- Addition of CD4+CD25+ lymphocytes significantly reduced the multiplicity of intestinal adenomas.
- The therapeutic effect of regulatory cells was dependent on Interleukin-10.
- Tumor regression was associated with increased apoptosis and down-regulation of cyclooxygenase-2 within the tumors.
Conclusions:
- Regulatory lymphocytes play a role in maintaining epithelial homeostasis in the ApcMin/+ mouse model.
- Interleukin-10 is crucial for the tumor-inhibitory function of these regulatory cells.
- These findings suggest potential broader applications for regulatory lymphocytes in preventing and treating human epithelial cancers.
