{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:58:11Z","timestamp":1774691891592,"version":"3.50.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tumor-infiltrating lymphocytes (TILs) are important prognostic factors in cancer progression and key players in cancer immunotherapy. Although \u03b3\u03b4 T lymphocytes can target a diversity of tumor cell types, their clinical manipulation is hampered by our limited knowledge of the molecular cues that determine \u03b3\u03b4 T cell migration toward tumors in vivo. In this study we set out to identify the chemotactic signals that orchestrate tumor infiltration by \u03b3\u03b4 T cells. We have used the preclinical transplantable B16 melanoma model to profile chemokines in tumor lesions and assess their impact on \u03b3\u03b4 TIL recruitment in vivo. We show that the inflammatory chemokine CCL2 and its receptor CCR2 are necessary for the accumulation of \u03b3\u03b4 TILs in B16 lesions, where they produce IFN-\u03b3 and display potent cytotoxic functions. Moreover, CCL2 directed \u03b3\u03b4 T cell migration in vitro toward tumor extracts, which was abrogated by anti-CCL2 neutralizing Abs. Strikingly, the lack of \u03b3\u03b4 TILs in TCR\u03b4-deficient but also in CCR2-deficient mice enhanced tumor growth in vivo, thus revealing an unanticipated protective role for CCR2\/CCL2 through the recruitment of \u03b3\u03b4 T cells. Importantly, we demonstrate that human V\u03b41 T cells, but not their V\u03b42 counterparts, express CCR2 and migrate to CCL2, whose expression is strongly deregulated in multiple human tumors of diverse origin, such as lung, prostate, liver, or breast cancer. This work identifies a novel protective role for CCL2\/CCR2 in the tumor microenvironment, while opening new perspectives for modulation of human V\u03b41 T cells in cancer immunotherapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1300434","type":"journal-article","created":{"date-parts":[[2013,5,18]],"date-time":"2013-05-18T04:37:56Z","timestamp":1368851876000},"page":"6673-6680","source":"Crossref","is-referenced-by-count":152,"title":["Protective Role of the Inflammatory CCR2\/CCL2 Chemokine Pathway through Recruitment of Type 1 Cytotoxic \u03b3\u03b4 T Lymphocytes to Tumor Beds"],"prefix":"10.1093","volume":"190","author":[{"given":"Telma","family":"Lan\u00e7a","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon,","place":["Portugal"]}]},{"given":"Maria Fernanda","family":"Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Aplicada, Farmanguinhos, Funda\u00e7\u00e3o Oswaldo Cruz , 21041-250 Rio de Janeiro,","place":["Brazil"]}]},{"given":"Natacha","family":"Gon\u00e7alves-Sousa","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon,","place":["Portugal"]}]},{"given":"Margarida","family":"Rei","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon,","place":["Portugal"]}]},{"given":"Ana Rita","family":"Grosso","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon,","place":["Portugal"]}]},{"given":"Carmen","family":"Penido","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Aplicada, Farmanguinhos, Funda\u00e7\u00e3o Oswaldo Cruz , 21041-250 Rio de Janeiro,","place":["Brazil"]},{"name":"Centro de Desenvolvimento Tecnol\u00f3gico em Sa\u00fade, Funda\u00e7\u00e3o Oswaldo Cruz , 21040-900 Rio de Janeiro,","place":["Brazil"]}]},{"given":"Bruno","family":"Silva-Santos","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon,","place":["Portugal"]},{"name":"Instituto Gulbenkian de Ci\u00eancia , 2780-156 Oeiras,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2013,6,15]]},"reference":[{"key":"2025032407074939200_r1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nri3191","article-title":"Adoptive immunotherapy for cancer: harnessing the T cell response","volume":"12","author":"Restifo","year":"2012","journal-title":"Nat. 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