{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:40:05Z","timestamp":1793209205026,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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-\u03b3 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.<\/jats:p>","DOI":"10.3390\/cancers12123723","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:45:36Z","timestamp":1607906736000},"page":"3723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The CCR2\/MCP-1 Chemokine Pathway and Lung Adenocarcinoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Payal","family":"Mittal","sequence":"first","affiliation":[{"name":"Chemical Biology, Medicinal Science Technology, GlaxoSmithKline, Collegeville, PA 19426, USA"},{"name":"Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Akimova","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Leach","sequence":"additional","affiliation":[{"name":"Chemical Biology, Medicinal Science Technology, GlaxoSmithKline, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose C.","family":"Clemente","sequence":"additional","affiliation":[{"name":"Chemical Biology, Medicinal Science Technology, GlaxoSmithKline, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Sender","sequence":"additional","affiliation":[{"name":"Chemical Biology, Medicinal Science Technology, GlaxoSmithKline, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Chemical Biology, Medicinal Science Technology, GlaxoSmithKline, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-8722","authenticated-orcid":false,"given":"Brandon J.","family":"Turunen","sequence":"additional","affiliation":[{"name":"Chemical Biology, Medicinal Science Technology, GlaxoSmithKline, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-5291","authenticated-orcid":false,"given":"Wayne W.","family":"Hancock","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ccell.2017.02.008","article-title":"Obstacles posed by the tumor microenvironment to T cell activity: A case for synergistic therapies","volume":"31","author":"Anderson","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3389\/fimmu.2018.00398","article-title":"Targeting myeloid-derived suppressor cells to bypass tumor-induced immunosuppression","volume":"9","author":"Fleming","year":"2018","journal-title":"Front. 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