{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T02:01:38Z","timestamp":1761789698687,"version":"3.37.3"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Solid tumors elicit suppressive T cell responses which impair antigen-presenting cell (APC) functions. Such immune suppression results in uncontrolled tumor growth and mortality. Addressing APC dysfunction, dendritic cell (DC)-mediated anti-tumor vaccination was extensively investigated in both mice and humans. These studies never achieved full resistance to tumor relapse. Herein, we describe a repetitive RM-1 murine tumor rechallenge model for recurrence in humans. Using this newly developed model, we show that priming with tumor antigen-pulsed, Toll-like receptor (TLR)2 ligand-activated DCs elicits a host-protective anti-tumor immune response in C57BL\/6 mice. Upon stimulation with the TLR2 ligand peptidoglycan (PGN), the tumor antigen-pulsed DCs induce complete resistance to repetitive tumor challenges. Intra-tumoral injection of PGN reduces tumor growth. The tumor resistance is accompanied by increased expression of interleukin (IL)-27, T-box transcription factor TBX21 (T-bet), IL-12, tumor necrosis factor (TNF)-\u03b1 and interferon (IFN)-\u03b3, along with heightened cytotoxic T lymphocyte (CTL) functions. Mice primed four times with PGN-stimulated tumor antigen-pulsed DCs remain entirely resistant to repeat challenges with RM-1 tumor cells, suggesting complete prevention of relapse and recurrence of tumor. Adoptive transfer of T cells from these mice, which were fully protected from RM-1 rechallenge, confers anti-tumor immunity to syngeneic naive recipient mice upon RM-1 challenge. These observations indicate that PGN-activated DCs induce robust host-protective anti-tumor T cells that completely resist tumor growth and recurrence.<\/jats:p>","DOI":"10.1111\/cei.13468","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T21:18:59Z","timestamp":1590182339000},"page":"279-288","source":"Crossref","is-referenced-by-count":4,"title":["Peptidoglycan-treated tumor antigen-pulsed dendritic cells impart complete resistance against tumor rechallenge"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-9680","authenticated-orcid":false,"given":"A","family":"Patidar","sequence":"first","affiliation":[{"name":"National Centre for Cell Science, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Pune, India"},{"name":"University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Chauhan","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C A","family":"Guzman","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Ebensen","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Trident Academy of Creative Technology, Bhubaneswar, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"National Institute of Traditional Medicine, Belagavi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-7912","authenticated-orcid":false,"given":"B","family":"Saha","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Pune, India"},{"name":"Trident Academy of Creative Technology, Bhubaneswar, India"},{"name":"National Institute of Traditional Medicine, Belagavi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"2021121023212611300_cei13468-bib-0001","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1084\/jem.189.5.753","article-title":"CD4 T cells and their role in antitumor immune responses","volume":"189","author":"Toes","year":"1999","journal-title":"J Exp Med"},{"key":"2021121023212611300_cei13468-bib-0002","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/sj.cdd.4402235","article-title":"The \u2018kiss of death\u2019 by dendritic cells to cancer cells","volume":"15","author":"Chan","year":"2008","journal-title":"Cell Death Differ"},{"key":"2021121023212611300_cei13468-bib-0003","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/0092-8674(89)90625-9","article-title":"Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ","volume":"56","author":"Thompson","year":"1989","journal-title":"Cell"},{"key":"2021121023212611300_cei13468-bib-0004","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cyto.2017.10.004","article-title":"DAMP\u2013TLR\u2013cytokine axis dictates the fate of tumor","volume":"104","author":"Patidar","year":"2017","journal-title":"Cytokine"},{"key":"2021121023212611300_cei13468-bib-0005","doi-asserted-by":"crossref","first-page":"5467","DOI":"10.1158\/0008-5472.CAN-10-3988","article-title":"TLR4 engagement during TLR3-induced proinflammatory signaling in dendritic cells promotes IL-10-mediated suppression of antitumor immunity","volume":"71","author":"Bogunovic","year":"2011","journal-title":"Cancer Res"},{"key":"2021121023212611300_cei13468-bib-0006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep17622","article-title":"TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma","volume":"5","author":"Damo","year":"2015","journal-title":"Sci Rep"},{"key":"2021121023212611300_cei13468-bib-0007","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cmi.2010.30","article-title":"The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice","volume":"7","author":"Ma","year":"2010","journal-title":"Cell Mol Immunol"},{"key":"2021121023212611300_cei13468-bib-0008","doi-asserted-by":"crossref","first-page":"12578","DOI":"10.1038\/srep12578","article-title":"A TLR9 agonist enhances the anti-tumor immunity of peptide and lipopeptide vaccines via different mechanisms","volume":"5","author":"Song","year":"2015","journal-title":"Sci Rep"},{"key":"2021121023212611300_cei13468-bib-0009","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1158\/2326-6066.CIR-13-0223","article-title":"Efficient induction of antitumor immunity by synthetic toll-like receptor ligand-peptide conjugates","volume":"2","author":"Zom","year":"2014","journal-title":"Cancer Immunol Res"},{"key":"2021121023212611300_cei13468-bib-0010","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1111\/j.1349-7006.2010.01583.x","article-title":"Adjuvant engineering for cancer immunotherapy: development of a synthetic TLR2 ligand with increased cell adhesion","volume":"101","author":"Akazawa","year":"2010","journal-title":"Cancer Sci"},{"key":"2021121023212611300_cei13468-bib-0011","doi-asserted-by":"crossref","first-page":"30804","DOI":"10.18632\/oncotarget.9001","article-title":"A Toll-like receptor 2 agonist-fused antigen enhanced antitumor immunity by increasing antigen presentation and the CD8 memory T cells population","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"2021121023212611300_cei13468-bib-0012","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1158\/2326-6066.CIR-18-0020","article-title":"TLR2 promotes glioma immune evasion by downregulating MHC class II molecules in microglia","volume":"6","author":"Qian","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"2021121023212611300_cei13468-bib-0013","doi-asserted-by":"crossref","first-page":"e18833","DOI":"10.1371\/journal.pone.0018833","article-title":"TLR2-dependent induction of IL-10 and Foxp3+ CD25+ CD4+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo","volume":"6","author":"Yamazaki","year":"2011","journal-title":"PLOS ONE"},{"key":"2021121023212611300_cei13468-bib-0014","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.4049\/jimmunol.1400672","article-title":"Pegylated bisacycloxypropylcysteine, a diacylated lipopeptide ligand of TLR6, plays a host-protective role against experimental leishmania major infection","volume":"193","author":"Pandey","year":"2014","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0015","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1084\/jem.190.5.617","article-title":"Distinct role of antigen-specific T helper type 1 (Th1) and Th2 cells in tumor eradication in vivo","volume":"190","author":"Nishimura","year":"1999","journal-title":"J Exp Med"},{"key":"2021121023212611300_cei13468-bib-0016","doi-asserted-by":"crossref","first-page":"6642","DOI":"10.4049\/jimmunol.177.10.6642","article-title":"Functional dichotomy in CD40 reciprocally regulates effector T cell functions","volume":"177","author":"Murugaiyan","year":"2006","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0017","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.4049\/jimmunol.178.4.2047","article-title":"Differential CD40\/CD40L expression results in counteracting antitumor immune responses","volume":"178","author":"Murugaiyan","year":"2007","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0018","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1002\/ijc.28833","article-title":"Anti-VEGF antibody enhances the antitumor effect of CD40","volume":"135","author":"Selvaraj","year":"2014","journal-title":"Int J Can"},{"key":"2021121023212611300_cei13468-bib-0019","doi-asserted-by":"crossref","first-page":"7317","DOI":"10.4049\/jimmunol.176.12.7317","article-title":"Antiangiogenic and antitumor activities of IL-27","volume":"176","author":"Shimizu","year":"2006","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0020","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.3390\/cancers3043856","article-title":"Cytokines in cancer immunotherapy","volume":"3","author":"Lee","year":"2011","journal-title":"Cancers"},{"key":"2021121023212611300_cei13468-bib-0021","doi-asserted-by":"crossref","first-page":"e1039763","DOI":"10.1080\/2162402X.2015.1039763","article-title":"Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells","volume":"5","author":"Haabeth","year":"2016","journal-title":"Oncoimmunology"},{"key":"2021121023212611300_cei13468-bib-0022","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2174\/157339506778018523","article-title":"Reversal of tumor induced dendritic cell paralysis: a treatment regimen against cancer","volume":"2","author":"Murugaiyan","year":"2006","journal-title":"Curr Immunol Rev"},{"key":"2021121023212611300_cei13468-bib-0023","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.trecan.2017.12.007","article-title":"Re-emergence of dendritic cell vaccines for cancer treatment","volume":"4","author":"Saxena","year":"2018","journal-title":"Trends Cancer"},{"key":"2021121023212611300_cei13468-bib-0024","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.4049\/jimmunol.165.7.3797","article-title":"Dendritic cells capture killed tumor cells and present their antigens to elicit tumor-specific immune responses","volume":"165","author":"Nouri-Shirazi","year":"2000","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0025","doi-asserted-by":"crossref","first-page":"5838","DOI":"10.4049\/jimmunol.162.10.5838","article-title":"Tumor antigens are constitutively presented in the draining lymph nodes","volume":"162","author":"Marzo","year":"1999","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0026","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev.immunol.18.1.245","article-title":"Dendritic cells in cancer immunotherapy","volume":"18","author":"Fong","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"2021121023212611300_cei13468-bib-0027","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fimmu.2018.00014","article-title":"Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy","volume":"9","author":"Durgeau","year":"2018","journal-title":"Front Immunol"},{"key":"2021121023212611300_cei13468-bib-0028","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.4049\/jimmunol.164.7.3645","article-title":"Crucial role of TNF-alpha in CD8 T cell-mediated elimination of 3LL-A9 Lewis lung carcinoma cells in vivo","volume":"164","author":"Pr\u00e9vost-Blondel","year":"2000","journal-title":"J Immunol"},{"key":"2021121023212611300_cei13468-bib-0029","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"2021121023212611300_cei13468-bib-0030","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"2021121023212611300_cei13468-bib-0031","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0165-2478(02)00228-6","article-title":"Recognition of pathogen-associated molecular patterns by TLR family","volume":"85","author":"Akira","year":"2003","journal-title":"Immunol Lett"},{"key":"2021121023212611300_cei13468-bib-0032","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/bjd.13236","article-title":"Aldara(\u00ae)-induced skin inflammation: studies of patients with psoriasis","volume":"172","author":"Vinter","year":"2015","journal-title":"Br J Dermatol"},{"key":"2021121023212611300_cei13468-bib-0033","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/cas.13576","article-title":"Development of a vaccine based on bacteria-mimicking tumor cells coated with novel engineered Toll-like receptor 2 ligands","volume":"109","author":"Akazawa","year":"2018","journal-title":"Cancer Sci"},{"key":"2021121023212611300_cei13468-bib-0034","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1158\/1078-0432.CCR-13-1432","article-title":"\u2018License to kill\u2019 reflects joint action of CD4 and CD8 T cells","volume":"19","author":"Melief","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2021121023212611300_cei13468-bib-0035","first-page":"343","article-title":"Dendritic cell-based immunotherapy: a promising approach for treatment of cancer","volume":"9","author":"Murugaiyan","year":"2005","journal-title":"Gene Ther Mol Biol"},{"key":"2021121023212611300_cei13468-bib-0036","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/ni1141","article-title":"Plasmacytoid dendritic cells in immunity","volume":"5","author":"Colonna","year":"2004","journal-title":"Nat Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.13468","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cei.13468","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cei.13468","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/201\/3\/279\/41636004\/cei13468.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/201\/3\/279\/41636004\/cei13468.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T11:35:02Z","timestamp":1696160102000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/201\/3\/279\/6403136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,26]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,6,26]]},"published-print":{"date-parts":[[2020,8,12]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13468","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"type":"print","value":"0009-9104"},{"type":"electronic","value":"1365-2249"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,6,26]]}}}