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


METHODS
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.
Department of Urology and Prostate Disease Center, University of Florida, Gainesville, FL 32610, USA.
Evgeniy
E
Eruslanov
Taryn
T
Stoffs
Wan-Ju
WJ
Kim
Irina
I
Daurkin
Scott M
SM
Gilbert
Li-Ming
LM
Su
Johannes
J
Vieweg
Yehia
Y
Daaka
Sergei
S
Kusmartsev
D039481:CD11b Antigen / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D054402:Chemokine CCL1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear; D022423:Myeloid Cells / Q000378:metabolism*; D054401:Receptors, CCR8 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D039481:CD11b Antigen; D054402:Chemokine CCL1; D054401:Receptors, CCR8