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Cancer Immunology, Immunotherapy

, Volume 63, Issue 8, pp 807–819 | Cite as

Altered chemokine production and accumulation of regulatory T cells in intestinal adenomas of APCMin/+ mice

  • Paulina AkeusEmail author
  • Veronica Langenes
  • Astrid von Mentzer
  • Ulf Yrlid
  • Åsa Sjöling
  • Pushpa Saksena
  • Sukanya Raghavan
  • Marianne Quiding-Järbrink
Original Article

Abstract

Tumor progression in the colon moves from aberrant crypt foci to adenomatous polyps to invasive carcinomas. The composition of the tumor-infiltrating leukocyte population affects the ability of the immune system to fight the tumor. T cell infiltration into colorectal adenocarcinomas, particularly T helper 1 (Th1) type T cells as well as increased regulatory T cell (Treg) frequencies, is correlated with improved prognosis. However, whether Th1 cells and Tregs are already present at the adenoma stage is not known. In this study, the APCMin/+ mouse model of intestinal adenomatous polyposis was used to investigate tumor-associated lymphocyte subsets and the mechanisms of their accumulation into gastrointestinal adenomas. Compared to unaffected tissue, adenomas accumulated CD4+FoxP3+ putative Treg in parallel with lower frequencies of conventional T cells and B cells. The accumulation of Treg was also observed in human adenomatous polyps. Despite high Treg numbers, the function of conventional T cells present in the APCMin/+ adenomas was not different from those in the unaffected tissue. Adenomas displayed an altered chemokine balance, with higher CCL17 and lower CXCL11 and CCL25 expression than in the unaffected tissue. In parallel, CXCR3+ Tregs were largely absent from adenomas. The data indicate that already in early stages of tumor development, the balance of lymphocyte-recruiting chemokines is altered possibly contributing to the observed shift toward higher frequencies of Treg.

Keywords

Regulatory T cells Tumor-infiltrating lymphocytes Colorectal cancer APCMin/+ Anti-tumor immunity Chemokines 

Abbreviations

APC

Adenomatous polyposis coli

CRC

Colorectal cancer

LPL

Lamina propria lymphocytes

MAdCAM-1

Mucosal addressin cellular adhesion molecule-1

MLN

Mesenteric lymph node

PLN

Peripheral lymph node

PMA

Phorbol myristate acetate

SI

Small intestine

Treg

Regulatory T cell

VCAM-1

Vascular cell adhesion molecule-1

WT

Wild-type

Notes

Acknowledgments

The authors would like to thank all patients who participated in the study. The study was supported by grants from the Swedish Research Council, the Swedish Cancer Foundation, the Sahlgrenska University Hospital, the Swedish Society of Medicine, the Ruth and Richard Julin foundation, Assar Gabrielssons foundation, Wilhelm and Martina Lundgren’s foundation, Sigurd and Elsa Goljes foundation, Olle Engkvist´s foundation and Hvitfeldska foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2014_1555_MOESM1_ESM.pdf (293 kb)
Supplementary material 1 (PDF 293 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Paulina Akeus
    • 1
    Email author
  • Veronica Langenes
    • 1
  • Astrid von Mentzer
    • 1
  • Ulf Yrlid
    • 1
  • Åsa Sjöling
    • 1
  • Pushpa Saksena
    • 2
  • Sukanya Raghavan
    • 1
  • Marianne Quiding-Järbrink
    • 1
  1. 1.Department of Microbiology and Immunology, Institute of BiomedicineSahlgrenska Academy at University of GothenburgGothenburgSweden
  2. 2.Department of PathologyUppsala UniversityUppsalaSweden

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