Allan B Dietz

Dennis A Gastineau

Michael P Gustafson

Peggy A Bulur

Yi Lin

Zhe (Jenny) Zhang

Journal for ImmunoTherapy of Cancer

PubMed

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Tumor monocyte cross talk promotes lymphoma
cell resistance to chemotherapy
Zhe (Jenny) Zhang1*, Peggy A Bulur2, Michael P Gustafson2, Dennis A Gastineau1,2, Allan B Dietz2,3, Yi Lin1
From Society for Immunotherapy of Cancer 28th Annual Meeting
National Harbor, MD, USA. 8-10 November 2013
Background
Immune editing is a major mechanism used by tumors
to promote its survival. We have reported previously the
presence of a novel phenotype of immunosuppressive
monocytes (CD14+HLA-DR low/neg) in a number of
cancers. Increased presence of these cells was associated
with decreased treatment response and OS. Here we
report an in vitro model to examine tumor monocyte
cross talk and demonstrate that these monocytes may
directly promote tumor cells’ resistance to chemotherapy.
Method
Monocytes from healthy donors were co-cultured with
lymphoma cell lines (OCI-Ly1, OCI-Ly3, OCI-Ly7, OCI-
Ly10, Su-DHL2, Su-DHL6, Jeko-1, Granta-519) with or
without doxorubicin (DOX). Cultured cells were assessed
for phenotype, viability and proliferation.
Results
Monocytes converted to CD14+HLA-DRlow/neg pheno-
type by co-culture with B cell lymphoma lines in 5 of the
8 cell lines tested. B cells from healthy donors did not
down regulate HLA-DR expression. The HLA-DR sup-
pression was not due to the known regulatory effects of
IL-10 as we found no correlation between the decreased
monocyte HLA-DR expression and IL-10 concentration
in supernatants. Thus, the magnitude of DR loss is
mediated by a yet undetermined mechanism. DOX incu-
bation induced apoptosis, decreased viability and pre-
vented proliferation of all of the cell lines. Co-culture
with monocytes improved the lymphoma cell survival in
3 of the 4 lymphoma cell lines (for example, untreated
Granta-519 had a 2.1±0.45 fold expansion, that
was reduced to 0.39±0.12 when treated with DOX and
0.81±0.27 after co-culture with monocytes with DOX.
p<0.05, n=11.) Lymphoma cells co-cultured with mono-
cytes had increased arginase I expression. This pheno-
mena was further increased in with DOX and monocyte
co-cultures.
Conclusions
We have demonstrated that certain tumor cells induce
phenotype changes in monocytes in an IL-10 indepen-
dent and a tumor specific way. In those cells where
tumors factors mediate monocyte phenotype, the mono-
cytes can promote tumor cell resistance to cytotoxic
killing by DOX, thus demonstrating a cross-talk between
monocyte and tumor function. We have shown pre-
viously that CD14+HLA-DRlow/neg monocytes can sup-
press lymphocyte function mediated partially through
arginase I expression. We found that in an environment
of monocyte/tumor cross talk, ARG 1 expression is
further increased in a cytotoxic environment. Together,
this data demonstrates an active cross talk between
monocytes and tumors resulting in multiple mechanisms
of tumor resistance to chemotherapy.
Authors’ details
1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester,
MN, USA. 2Division of Transfusion Medicine, Department of Laboratory
Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 3Division of
Experimental Pathology, Mayo Clinic, Rochester, MN, USA.
Published: 7 November 2013
doi:10.1186/2051-1426-1-S1-P179
Cite this article as: Zhang et al.: Tumor monocyte cross talk promotes
lymphoma cell resistance to chemotherapy. Journal for ImmunoTherapy
of Cancer 2013 1(Suppl 1):P179.
1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester,
MN, USA
Full list of author information is available at the end of the article
Zhang et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P179
http://www.immunotherapyofcancer.org/content/1/S1/P179
© 2013 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


Tumor monocyte cross talk promotes lymphoma cell resistance to chemotherapy

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Tumor monocyte cross talk promotes lymphoma cell resistance to chemotherapy

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