Title

Expansion of CCR8(+) inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas.

Authors

Evgeniy Eruslanov
Taryn Stoffs
Wan-Ju Kim
Irina Daurkin
Scott M Gilbert
Li-Ming Su
Johannes Vieweg, Nova Southeastern UniversityFollow
Yehia Daaka
Sergei Kusmartsev

ISBN or ISSN

1078-0432

Publication Title

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

19

Issue

7

Publication Date / Copyright Date

4-1-2013

First Page

1670

Last Page

1680

Publisher

American Association for Cancer Research

DOI Number

10.1158/1078-0432.CCR-12-2091

Abstract

PURPOSE: Chemokines are involved in cancer-related inflammation and malignant progression. In this study, we evaluated expression of CCR8 and its natural cognate ligand CCL1 in patients with urothelial carcinomas of bladder and renal cell carcinomas.

EXPERIMENTAL DESIGN: We examined CCR8 expression in peripheral blood and tumor tissues from patients with bladder and renal carcinomas. CCR8-positive myeloid cells were isolated from cancer tissues with magnetic beads and tested in vitro for cytokine production and ability to modulate T-cell function.

RESULTS: We show that monocytic and granulocytic myeloid cell subsets in peripheral blood of patients with cancer with urothelial and renal carcinomas display increased expression of chemokine receptor CCR8. Upregulated expression of CCR8 is also detected within human cancer tissues and primarily limited to tumor-associated macrophages. When isolated, CD11b(+)CCR8(+) cell subset produces the highest levels of proinflammatory and proangiogenic factors among intratumoral CD11b myeloid cells. Tumor-infiltrating CD11b(+)CCR8(+) cells selectively display activated Stat3 and are capable of inducing FoxP3 expression in autologous T lymphocytes. Primary human tumors produce substantial amounts of the natural CCR8 ligand CCL1.

CONCLUSIONS: This study provides the first evidence that CCR8(+) myeloid cell subset is expanded in patients with cancer. Elevated secretion of CCL1 by tumors and increased presence of CCR8(+) myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion. Obtained results also implicate that blockade of CCR8 signals may provide an attractive strategy for therapeutic intervention in human urothelial and renal cancers.

Disciplines

Medicine and Health Sciences

Keywords

CD11b Antigen, Carcinoma, Chemokine CCL1, Humans, Inflammation, Kidney Neoplasms, Leukocytes, Mononuclear, Myeloid Cells, Receptors, CCR8, Urinary Bladder Neoplasms

NSUWorks Citation

Eruslanov, Evgeniy; Stoffs, Taryn; Kim, Wan-Ju; Daurkin, Irina; Gilbert, Scott M; Su, Li-Ming; Vieweg, Johannes; Daaka, Yehia; and Kusmartsev, Sergei, "Expansion of CCR8(+) inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas." (2013). NSU-MD Faculty Articles. 64.
https://nsuworks.nova.edu/hpd_md_facarticles/64