{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:59:01Z","timestamp":1789664341592,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001513","name":"Cancer Society of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001513","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p>The chemotherapeutic drug 5,6\u2010dimethylxanthenone\u20104\u2010acetic acid (DMXAA) inhibits intratumoural blood flow, causing hypoxia, haemorrhagic necrosis, vascular collapse and tumour cell death. Production of TNF\u2010\u03b1 and IFN is also induced, causing local inflammation and activation of immune cells including CD8<jats:sup>+<\/jats:sup> T cells. We used the tumour cell line LL\u2010LCMV, which expresses the gp33 epitope of lymphocytic choriomeningitis virus in a non\u2010immunogenic form, to investigate whether tumour cell death caused by treatment with DMXAA may improve the success of tumour immunotherapy mediated by CD8<jats:sup>+<\/jats:sup> T cells. Treatment with DMXAA was effective at reducing the size of LL\u2010LCMV tumours. However, compared to normal mice, tumour reduction was no more marked or sustained in mice carrying high numbers of naive, tumour\u2010specific CD8<jats:sup>+<\/jats:sup> T cells. The antitumour effect of activated CD8<jats:sup>+<\/jats:sup> T cells was also not affected by DMXAA treatment. Tumour\u2010specific CD8<jats:sup>+<\/jats:sup> T cells activated <jats:italic>in vivo<\/jats:italic> by immunization with dendritic cells and specific tumour peptide antigen, or generated <jats:italic>in vitro<\/jats:italic> and adoptively transferred into tumour\u2010bearing mice by i.v. injection, did not improve or sustain the reduction in tumour size induced by DMXAA treatment. We conclude that the presence of high numbers of naive CD8<jats:sup>+<\/jats:sup> T cells, or immunotherapies leading to CD8<jats:sup>+<\/jats:sup> T\u2010cell activation, do not synergize with the tumour cell death and local inflammation induced by DMXAA treatment. It is possible that this lack of synergism may result from both treatments inducing activation of CD8<jats:sup>+<\/jats:sup> T cells and that treatments that activate different populations of immune cells may achieve better success.<\/jats:p>","DOI":"10.1111\/j.1440-1711.2006.01448.x","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T12:08:40Z","timestamp":1146053320000},"page":"383-389","source":"Crossref","is-referenced-by-count":12,"title":["5,6\u2010Dimethylxanthenone\u20104\u2010acetic acid treatment of a non\u2010immunogenic tumour does not synergize with active or passive CD8<sup>+<\/sup> T\u2010cell immunotherapy"],"prefix":"10.1111","volume":"84","author":[{"given":"Kate E","family":"Matthews","sequence":"first","affiliation":[{"name":"Malaghan Institute of Medical Research  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian F","family":"Hermans","sequence":"additional","affiliation":[{"name":"Malaghan Institute of Medical Research  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna M","family":"Roberts","sequence":"additional","affiliation":[{"name":"Malaghan Institute of Medical Research  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai\u2010Ming","family":"Ching","sequence":"additional","affiliation":[{"name":"Cancer Society Research Centre, The University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Ronchese","sequence":"additional","affiliation":[{"name":"Malaghan Institute of Medical Research  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1297"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002620050392"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.512"},{"key":"e_1_2_7_5_1","first-page":"79","article-title":"Correlation between immune and vascular activities of xanthenone acetic acid antitumor agents","volume":"6","author":"Zwi LJ","year":"1994","journal-title":"Oncol. Res."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(03)01018-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600368"},{"key":"e_1_2_7_8_1","first-page":"4582","article-title":"Scintigraphic imaging of the hypoxia marker (99m)technetium\u2010labeled 2, 2\u2032\u2010(1,4\u2010diaminobutane)bis(2\u2010methyl\u20103\u2010butanone) dioxime (99mTc\u2010labeled HL\u201091; prognox): noninvasive detection of tumor response to the antivascular agent 5,6\u2010dimethylxanthenone\u20104\u2010acetic acid","volume":"60","author":"Siim BG","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_7_9_1","first-page":"3304","article-title":"Induction of intratumoral tumor necrosis factor (TNF) synthesis and hemorrhagic necrosis by 5,6\u2010dimethylxanthenone\u20104\u2010acetic acid (DMXAA) in TNF knockout mice","volume":"59","author":"Ching LM","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_10_1","first-page":"633","article-title":"Stimulation of tumors to synthesize tumor necrosis factor\u2010alpha in situ using 5,6\u2010dimethylxanthenone\u20104\u2010acetic acid: a novel approach to cancer therapy","volume":"59","author":"Joseph WR","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600479"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.10.4684"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(98)00050-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390702"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"592","DOI":"10.4049\/jimmunol.146.2.592","article-title":"Tumor necrosis factor combines with IL\u20104 or IFN\u2010gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule\u20101\u2010dependent and \u2010independent binding mechanisms","volume":"146","author":"Thornhill MH","year":"1991","journal-title":"J. Immunol."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2738"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0202-157"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.5.1277"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90775-7"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V76.5.965.965"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1991.12"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1992.228"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0277-5379(90)90056-Y"},{"key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"11 752","DOI":"10.1158\/0008-5472.CAN-05-1658","article-title":"Activation of tumor\u2010associated macrophages by the vascular disrupting agent 5,6\u2010dimethylxanthenone\u20104\u2010acetic acid induces an effective CD8+ T\u2010cell\u2010mediated antitumor immune response in murine models of lung cancer and mesothelioma","volume":"65","author":"Jassar AS","year":"2005","journal-title":"Cancer Res."},{"key":"e_1_2_7_25_1","first-page":"3909","article-title":"Antigen expressed on tumor cells fails to elicit an immune response, even in the presence of increased numbers of tumor\u2010specific cytotoxic T lymphocyte precursors","volume":"58","author":"Hermans IF","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/342559a0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.9.3508.bloodjournal8893508"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6497"},{"key":"e_1_2_7_29_1","first-page":"291","article-title":"Resistance of cultured Lewis lung carcinoma cell lines to tiazofurin","volume":"79","author":"Finlay GJ","year":"1987","journal-title":"J. Natl Cancer Inst."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.767"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.245"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00689199"},{"key":"e_1_2_7_33_1","first-page":"257","article-title":"Dermal tumour necrosis factor\u2010alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans\u2019 cell migration","volume":"75","author":"Cumberbatch M","year":"1992","journal-title":"Immunology"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00360.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096378"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096268"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03290"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1201"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80163-6"},{"key":"e_1_2_7_40_1","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.4049\/jimmunol.140.9.3261","article-title":"Flavone\u20108\u2010acetic acid augments systemic natural killer cell activity and synergizes with IL\u20102 for treatment of murine renal cancer","volume":"140","author":"Wiltrout RH","year":"1988","journal-title":"J. Immunol."},{"key":"e_1_2_7_41_1","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.4049\/jimmunol.141.10.3671","article-title":"Augmentation of natural killer activity, induction of IFN and development tumor immunity during the successful treatment of established murine renal cancer using flavone acetic acid and IL\u20102","volume":"141","author":"Hornung RL","year":"1988","journal-title":"J. Immunol."},{"key":"e_1_2_7_42_1","first-page":"1948","article-title":"Vascular attack by 5,6\u2010dimethylxanthenone\u20104\u2010acetic acid combined with B7.1 (CD80)\u2010mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci","volume":"61","author":"Kanwar JR","year":"2001","journal-title":"Cancer Res."}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1440-1711.2006.01448.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1440-1711.2006.01448.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/j.1440-1711.2006.01448.x","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1440-1711.2006.01448.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:19:00Z","timestamp":1694038740000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1440-1711.2006.01448.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,8]]}},"alternative-id":["10.1111\/j.1440-1711.2006.01448.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1440-1711.2006.01448.x","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,8]]}}}