Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/29641
Full metadata record
DC FieldValueLanguage
dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP-
dc.contributor.authorWANDERLEY, Carlos W.-
dc.contributor.authorCOLON, David F.-
dc.contributor.authorLUIZ, Joao Paulo M.-
dc.contributor.authorOLIVEIRA, Francisco F.-
dc.contributor.authorVIACAVA, Paula R.-
dc.contributor.authorLEITE, Caio A.-
dc.contributor.authorPEREIRA, Janaina A.-
dc.contributor.authorSILVA, Camila M.-
dc.contributor.authorSILVA, Cassia R.-
dc.contributor.authorSILVA, Rangel L.-
dc.contributor.authorSPECK-HERNANDEZ, Cesar A.-
dc.contributor.authorMOTA, Jose M.-
dc.contributor.authorALVES-FILHO, Jose C.-
dc.contributor.authorLIMA-JUNIOR, Roberto C.-
dc.contributor.authorCUNHA, Thiago M.-
dc.contributor.authorCUNHA, Fernando Q.-
dc.date.accessioned2018-11-21T17:09:08Z-
dc.date.available2018-11-21T17:09:08Z-
dc.date.issued2018-
dc.identifier.citationCANCER RESEARCH, v.78, n.20, p.5891-5900, 2018-
dc.identifier.issn0008-5472-
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/29641-
dc.description.abstractPaclitaxel is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of paclitaxel is based on microtubule stabilization inducing cell-cycle arrest. Here, we use several tumor models to show that paclitaxel not only induces tumor cell-cycle arrest, but also promotes antitumor immunity. In vitro, paclitaxel reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. Paclitaxel also modulated the tumor-associated macrophage (TAM) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that paclitaxel altered the M2-like signature of TAMs toward an M1-like profile. In mice selectively lacking TLR4 on myeloid cells, for example, macrophages (LysM-Cre(+/-)/TLR4(fl/fl)), the antitumor effect of paclitaxel was attenuated. Gene expression analysis of tumor samples from patients with ovarian cancer before and after treatment with paclitaxel detected an enrichment of genes linked to the M1 macrophage activation profile (IFN gamma-stimulated macrophages). These findings indicate that paclitaxel skews TAMs toward an immunocompetent profile via TLR4, which might contribute to the antitumor effect of paclitaxel and provide a rationale for new combination regimens comprising paclitaxel and immunotherapies as an anticancer treatment. Significance: This study provides new evidence that the antitumor effect of paclitaxel occurs in part via reactivation of the immune response against cancer, guiding tumor-associated macrophages toward the M1-like antitumor phenotype. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5891/F1.large.jpg. (C) 2018 AACR.-
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP) [2013/08216-2]-
dc.description.sponsorshipConselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq)-
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)-
dc.language.isoeng-
dc.publisherAMER ASSOC CANCER RESEARCH-
dc.relation.ispartofCancer Research-
dc.rightsrestrictedAccess-
dc.subject.otherperitoneal-macrophages-
dc.subject.otheranticancer therapies-
dc.subject.othergene-expression-
dc.subject.otherbreast-cancer-
dc.subject.otheractivation-
dc.subject.otherlipopolysaccharide-
dc.subject.othertlr4-
dc.subject.otherpolarization-
dc.subject.otherresponses-
dc.subject.othercells-
dc.titlePaclitaxel Reduces Tumor Growth by Reprogramming Tumor-Associated Macrophages to an M1 Profile in a TLR4-Dependent Manner-
dc.typearticle-
dc.rights.holderCopyright AMER ASSOC CANCER RESEARCH-
dc.identifier.doi10.1158/0008-5472.CAN-17-3480-
dc.identifier.pmid30104241
dc.subject.wosOncology-
dc.type.categoryoriginal article-
dc.type.versionpublishedVersion-
hcfmusp.author.externalWANDERLEY, Carlos W.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil; Univ Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara, Brazil-
hcfmusp.author.externalCOLON, David F.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalLUIZ, Joao Paulo M.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalOLIVEIRA, Francisco F.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil; Univ Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara, Brazil-
hcfmusp.author.externalVIACAVA, Paula R.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalLEITE, Caio A.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalPEREIRA, Janaina A.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalSILVA, Camila M.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil; Univ Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara, Brazil-
hcfmusp.author.externalSILVA, Cassia R.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil; Univ Fed Uberlandia, Biotechnol Inst, Uberlandia, MG, Brazil-
hcfmusp.author.externalSILVA, Rangel L.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalSPECK-HERNANDEZ, Cesar A.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalALVES-FILHO, Jose C.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalLIMA-JUNIOR, Roberto C.:Univ Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara, Brazil-
hcfmusp.author.externalCUNHA, Thiago M.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.author.externalCUNHA, Fernando Q.:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil-
hcfmusp.description.beginpage5891-
hcfmusp.description.endpage5900-
hcfmusp.description.issue20-
hcfmusp.description.volume78-
hcfmusp.origemWOS-
hcfmusp.origem.idWOS:000447552500015-
hcfmusp.origem.id2-s2.0-85054890462-
hcfmusp.publisher.cityPHILADELPHIA-
hcfmusp.publisher.countryUSA-
hcfmusp.relation.referenceApetoh L, 2007, NAT MED, V13, P1050, DOI 10.1038/nm1622-
hcfmusp.relation.referenceAuthier H, 2008, INT J PARASITOL, V38, P341, DOI 10.1016/j.ijpara.2007.08.002-
hcfmusp.relation.referenceBiswas SK, 2010, NAT IMMUNOL, V11, P889, DOI 10.1038/ni.1937-
hcfmusp.relation.referenceBoussios S, 2012, ANN GASTROENTEROL, V25, P106-
hcfmusp.relation.referenceBronte V, 2015, NAT MED, V21, P117, DOI 10.1038/nm.3794-
hcfmusp.relation.referenceCassidy PB, 2002, CLIN CANCER RES, V8, P846-
hcfmusp.relation.referenceChicoine MR, 2007, NEUROSURGERY, V60, P372, DOI 10.1227/01.NEU.0000249280.61761.2E-
hcfmusp.relation.referenceChoudhary MM, 2016, WORLD J OTORHINO HN, V2, P90, DOI 10.1016/J.WJORL.2016.05.002-
hcfmusp.relation.referenceDavar D, 2013, CLIN DERMATOL, V31, P237, DOI 10.1016/j.clindermatol.2012.08.012-
hcfmusp.relation.referenceDavis MB, 2011, CLIN CANCER RES, V17, P3984, DOI 10.1158/1078-0432.CCR-10-3262-
hcfmusp.relation.referenceDe Palma M, 2013, CANCER CELL, V23, P277, DOI 10.1016/j.ccr.2013.02.013-
hcfmusp.relation.referenceFang HL, 2014, CELL MOL IMMUNOL, V11, P150, DOI 10.1038/cmi.2013.59-
hcfmusp.relation.referenceGhiringhelli F, 2004, EUR J IMMUNOL, V34, P336, DOI 10.1002/eji.200324181-
hcfmusp.relation.referenceGodec J, 2016, IMMUNITY, V44, P194, DOI 10.1016/j.immuni.2015.12.006-
hcfmusp.relation.referenceGoel S, 2017, NATURE, V548, P471, DOI 10.1038/nature23465-
hcfmusp.relation.referenceGonzalez-Martin A, 2014, CLIN TRANSL ONCOL, V16, P1067, DOI 10.1007/s12094-014-1229-z-
hcfmusp.relation.referenceGoto S, 1996, CANCER IMMUNOL IMMUN, V42, P255, DOI 10.1007/s002620050279-
hcfmusp.relation.referenceGuerriero JL, 2017, NATURE, V543, P428, DOI 10.1038/nature21409-
hcfmusp.relation.referenceGuo H, 2016, CANCER IMMUNOL IMMUN, V65, P677, DOI 10.1007/s00262-016-1824-7-
hcfmusp.relation.referenceKawasaki K, 2001, J ENDOTOXIN RES, V7, P232, DOI 10.1179/096805101101532738-
hcfmusp.relation.referenceLadoire S, 2011, J PATHOL, V224, P389, DOI 10.1002/path.2866-
hcfmusp.relation.referenceLi Y, 2015, J NEUROSCI, V35, P13487, DOI 10.1523/JNEUROSCI.1956-15.2015-
hcfmusp.relation.referenceLizotte PH, 2014, ONCOIMMUNOLOGY, V3, DOI 10.4161/onci.28926-
hcfmusp.relation.referenceMajor J, 2002, J IMMUNOL, V168, P2456, DOI 10.4049/jimmunol.168.5.2456-
hcfmusp.relation.referenceMANTOVANI A, 1979, J NATL CANCER I, V63, P61-
hcfmusp.relation.referenceMantovani A, 2004, TRENDS IMMUNOL, V25, P677, DOI 10.1016/j.it.2004.09.015-
hcfmusp.relation.referenceMcCarthy CG, 2014, AM J PHYSIOL-HEART C, V306, pH184, DOI 10.1152/ajpheart.00328.2013-
hcfmusp.relation.referenceMcCarthy Edward F, 2006, Iowa Orthop J, V26, P154-
hcfmusp.relation.referenceMosser DM, 2008, NAT REV IMMUNOL, V8, P958, DOI 10.1038/nri2448-
hcfmusp.relation.referenceMota JM, 2016, CANCER IMMUNOL RES, V4, P312, DOI 10.1158/2326-6066.CIR-15-0170-
hcfmusp.relation.referenceMurray PJ, 2014, IMMUNITY, V41, P14, DOI 10.1016/j.immuni.2014.06.008-
hcfmusp.relation.referenceNoy R, 2014, IMMUNITY, V41, P49, DOI 10.1016/j.immuni.2014.06.010-
hcfmusp.relation.referencePerera PY, 2001, J IMMUNOL, V166, P574, DOI 10.4049/jimmunol.166.1.574-
hcfmusp.relation.referencePfannenstiel LW, 2010, CELL IMMUNOL, V263, P79, DOI 10.1016/j.cellimm.2010.03.001-
hcfmusp.relation.referencePusztai L, 2004, CYTOKINE, V25, P94, DOI 10.1016/j.cyto.2003.10.004-
hcfmusp.relation.referencePyonteck SM, 2013, NAT MED, V19, P1264, DOI 10.1038/nm.3337-
hcfmusp.relation.referenceRajput S, 2013, MOL CANCER THER, V12, P1676, DOI 10.1158/1535-7163.MCT-12-1019-
hcfmusp.relation.referenceResman N, 2014, J IMMUNOL, V192, P1887, DOI 10.4049/jimmunol.1302119-
hcfmusp.relation.referenceRoy S, 2017, NAT REV CANCER, V17, P271, DOI 10.1038/nrc.2017.13-
hcfmusp.relation.referenceSchroder AJ, 2002, J IMMUNOL, V168, P996, DOI 10.4049/jimmunol.168.3.996-
hcfmusp.relation.referenceShear MJ, 1943, J NATL CANCER I, V4, P81-
hcfmusp.relation.referenceStout RD, 2005, J IMMUNOL, V175, P342, DOI 10.4049/jimmunol.175.1.342-
hcfmusp.relation.referenceViaud S, 2013, SCIENCE, V342, P971, DOI 10.1126/science.1240537-
hcfmusp.relation.referenceWang AC, 2009, EUR J CLIN INVEST, V39, P157, DOI 10.1111/j.1365-2362.2008.02070.x-
hcfmusp.relation.referenceWang N, 2014, FRONT IMMUNOL, V5, DOI 10.3389/fimmu.2014.00614-
hcfmusp.relation.referenceWhite CM, 1998, CANCER IMMUNOL IMMUN, V46, P104, DOI 10.1007/s002620050468-
hcfmusp.relation.referenceZhang Q, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0031230-
hcfmusp.relation.referenceZhu XX, 2017, J GYNECOL ONCOL, V28, DOI 10.3802/jgo.2017.28.e64-
hcfmusp.relation.referenceZitvogel L, 2013, IMMUNITY, V39, P74, DOI 10.1016/j.immuni.2013.06.014-
dc.description.indexMEDLINE-
dc.identifier.eissn1538-7445-
hcfmusp.citation.scopus161-
hcfmusp.scopus.lastupdate2022-06-16-
Appears in Collections:

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar


Files in This Item:
File Description SizeFormat 
art_WANDERLEY_Paclitaxel_Reduces_Tumor_Growth_by_Reprogramming_TumorAssociated_Macrophages_2018.PDF
  Restricted Access
publishedVersion (English)1.46 MBAdobe PDFView/Open Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.