{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T05:42:11Z","timestamp":1698730931771},"reference-count":66,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Given that metastasized melanoma is a fatal disease in most cases, it is tempting to develop strategies to <jats:italic>a priori<\/jats:italic> prevent metastasis. We have stimulated the pulmonary innate immune system by macrophage\u2010activating lipopeptide\u20102 (MALP\u20102), a specific agonist at Toll\u2010like receptor (TLR) 2\/6, and investigated its impact on experimental melanoma metastasis. In C57BL\/6 mice, intratracheal application of MALP\u20102 induced a profound influx of neutrophils and macrophages into the lung, which peaked after 24\u2003h (sixfold increase) and returned to baseline within 72\u2003h. Further analysis revealed that MALP\u20102 also markedly induced VCAM\u20101 expression on pulmonary blood vessels. <jats:italic>In vitro<\/jats:italic> experiments demonstrated that this adhesion molecule mediates binding of B16F10 melanoma cells. Furthermore, <jats:italic>in vivo<\/jats:italic> or <jats:italic>in vitro<\/jats:italic> treatment with MALP\u20102 did not significantly affect the ability of immune cells to lyse melanoma cells. As a consequence, notwithstanding the profound pulmonary immune response induction and in contrast to conclusions drawn from some previous publications, the net extent of experimental metastasis did not change significantly, regardless of the application regimen of MALP\u20102 prior to, concomitant with or after tumor cell inoculation. Melanoma cells stably transfected with green fluorescent protein allowed tracking of early events after tumor cell dissemination and showed that MALP\u20102\u2010mediated TLR2\/6 activation did not interfere with pulmonary melanoma cell arrest. Likewise, boosting the immune induction after establishment of metastases did not change the clinical outcome. These unexpected results vividly counsel caution regarding predictions of immunomodulating therapies, as multiple intertwined effects may influence the net outcome.<\/jats:p>","DOI":"10.1111\/j.1600-0625.2011.01386.x","type":"journal-article","created":{"date-parts":[[2011,10,11]],"date-time":"2011-10-11T06:53:03Z","timestamp":1318315983000},"page":"91-98","source":"Crossref","is-referenced-by-count":10,"title":["Stimulation of pulmonary immune responses by the TLR2\/6 agonist MALP\u20102 and effect on melanoma metastasis to the lung"],"prefix":"10.1111","volume":"21","author":[{"given":"Tillmann","family":"Schill","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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