Unknown

Dataset Information

0

The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma.


ABSTRACT: Host anti-tumor immunity can be hindered by various mechanisms present within the tumor microenvironment, including the actions of myeloid-derived suppressor cells (MDSCs). We investigated the role of the CCR2/MCP-1 pathway in MDSC-associated tumor progression in murine lung cancer models. Phenotypic profiling revealed maximal expression of CCR2 by tumor-resident MDSCs, and MCP-1 by transplanted TC1 tumor cells, respectively. Use of CCR2-knockout (CCR2-KO) mice showed dependence of tumor growth on CCR2 signaling. Tumors in CCR2-KO mice had fewer CCR2low MDSCs, CD4 T cells and Tregs than WT mice, and increased infiltration by CD8 T cells producing IFN-? and granzyme-B. Effects were MDSC specific, since WT and CCR2-KO conventional T (Tcon) cells had comparable proliferation and production of inflammatory cytokines, and suppressive functions of WT and CCR2-KO Foxp3+ Treg cells were also similar. We used a thioglycolate-induced peritonitis model to demonstrate a role for CCR2/MCP-1 in trafficking of CCR2+ cells to an inflammatory site, and showed the ability of a CCR2 antagonist to inhibit such trafficking. Use of this CCR2 antagonist promoted anti-tumor immunity and limited tumor growth. In summary, tumor cells are the prime source of MCP-1 that promotes MDSC recruitment, and our genetic and pharmacologic data demonstrate that CCR2 targeting may be an important component of cancer immunotherapy.

SUBMITTER: Mittal P 

PROVIDER: S-EPMC7763565 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


Host anti-tumor immunity can be hindered by various mechanisms present within the tumor microenvironment, including the actions of myeloid-derived suppressor cells (MDSCs). We investigated the role of the CCR2/MCP-1 pathway in MDSC-associated tumor progression in murine lung cancer models. Phenotypic profiling revealed maximal expression of CCR2 by tumor-resident MDSCs, and MCP-1 by transplanted TC1 tumor cells, respectively. Use of CCR2-knockout (CCR2-KO) mice showed dependence of tumor growth  ...[more]

Similar Datasets

| S-EPMC3617241 | biostudies-literature
| S-EPMC3885670 | biostudies-literature
| S-EPMC7028862 | biostudies-literature
| S-EPMC8620886 | biostudies-literature
| S-EPMC2864217 | biostudies-other
| S-EPMC5363634 | biostudies-other
| S-EPMC3528555 | biostudies-literature
| S-EPMC4336839 | biostudies-literature
2020-04-08 | PXD015845 | Pride
| S-EPMC4283412 | biostudies-literature