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Kaposi s sarcoma-associated herpesvirus infection promotes differentiation and
polarization of monocytes into tumor-associated macrophages
#MMPMID28750175
Bhaskaran N
; Ghosh SK
; Yu X
; Qin S
; Weinberg A
; Pandiyan P
; Ye F
Cell Cycle
2017[]; 16
(17
): 1611-1621
PMID28750175
show ga
Tumor associated macrophages (TAMs) promote angiogenesis, tumor invasion and
metastasis, and suppression of anti-tumor immunity. These myeloid cells originate
from monocytes, which differentiate into TAMs upon exposure to the local tumor
microenvironment. We previously reported that Kaposi's sarcoma-associated herpes
virus (KSHV) infection of endothelial cells induces the cytokine angiopoietin-2
(Ang-2) to promote migration of monocytes into tumors. Here we report that KSHV
infection of endothelial cells induces additional cytokines including
interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) that
drive monocytes to differentiate and polarize into TAMs. The KSHV-induced TAMs
not only express TAM-specific markers such as CD-163 and legumain (LGMN) but also
display a gene expression profile with characteristic features of viral
infection. More importantly, KSHV-induced TAMs enhance tumor growth in nude mice.
These results are consistent with the strong presence of TAMs in Kaposi's sarcoma
(KS) tumors. Therefore, KSHV infection of endothelial cells generates a local
microenvironment that not only promotes the recruitment of monocytes but also
induces their differentiation and polarization into TAMs. These findings reveal a
new mechanism of KSHV contribution to KS tumor development.
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