4.00
Hdl Handle:
http://hdl.handle.net/10033/621211
Title:
Therapeutic Potential of Bacteria against Solid Tumors.
Authors:
Hatzikirou, Haralampos; López Alfonso, Juan Carlos; Leschner, Sara; Weiss, Siegfried; Meyer-Hermann, Michael ( 0000-0002-4300-2474 )
Abstract:
Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects. Cancer Res; 77(7); 1553-63. ©2017 AACR.
Affiliation:
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
Citation:
Therapeutic Potential of Bacteria against Solid Tumors. 2017, 77 (7):1553-1563 Cancer Res.
Journal:
Cancer research
Issue Date:
1-Apr-2017
URI:
http://hdl.handle.net/10033/621211
DOI:
10.1158/0008-5472.CAN-16-1621
PubMed ID:
28202530
Type:
Article
Language:
en
ISSN:
1538-7445
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorHatzikirou, Haralamposen
dc.contributor.authorLópez Alfonso, Juan Carlosen
dc.contributor.authorLeschner, Saraen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorMeyer-Hermann, Michaelen
dc.date.accessioned2017-12-19T14:47:16Z-
dc.date.available2017-12-19T14:47:16Z-
dc.date.issued2017-04-01-
dc.identifier.citationTherapeutic Potential of Bacteria against Solid Tumors. 2017, 77 (7):1553-1563 Cancer Res.en
dc.identifier.issn1538-7445-
dc.identifier.pmid28202530-
dc.identifier.doi10.1158/0008-5472.CAN-16-1621-
dc.identifier.urihttp://hdl.handle.net/10033/621211-
dc.description.abstractIntentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects. Cancer Res; 77(7); 1553-63. ©2017 AACR.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshBacterial Infectionsen
dc.subject.meshBacterial Loaden
dc.subject.meshCell Line, Tumoren
dc.subject.meshDisease Models, Animalen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshModels, Theoreticalen
dc.subject.meshNeoplasmsen
dc.subject.meshTumor Burdenen
dc.subject.meshTumor Necrosis Factor-alphaen
dc.titleTherapeutic Potential of Bacteria against Solid Tumors.en
dc.typeArticleen
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.en
dc.identifier.journalCancer researchen
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