The Impact of Surgery-induced Inflammation on Anti-neoplastic Immunity and Metastasis

Visa enkel post
dc.contributor.authorHallgren, Beatrice
dc.contributor.departmentChalmers tekniska högskola / Institutionen för biologi och biotekniksv
dc.contributor.departmentChalmers University of Technology / Department of Biology and Biological Engineeringen
dc.date.accessioned2019-07-05T11:52:08Z
dc.date.available2019-07-05T11:52:08Z
dc.date.issued2019
dc.description.abstractThe trauma associated with cancer surgery may trigger the release of tumor cells into the blood stream along with a systemic inflammatory response that hampers immunosurveillance. Both these factors might enhance the risk of development of distant metastases. Myeloid cells express the NOX2-enzyme that generates reactive oxygen species (ROS) that participate in the clearance of pathogens. However, extracellularly released NOX2-derived ROS may also triggers dysfunction and apoptosis in adjacent anti-neoplastic lymphocytes. Myeloid cells produce enhanced levels of NOX2-derived reactive oxygen species (ROS) during infection, but also during inflammation and cancer. In this study, we explored the role for NOX2-derived ROS in surgery-induced immunosuppression and metastasis formation in vivo by the use of a wounding model. To mimic surgery-related inflammation, sterile polyvinyl alcohol (PVA) sponges were implanted s.c. to WT and NOX2-deficient (Nox2-/-) mice one week before injection of B16F10 melanoma cells into the blood stream. The presence of implanted sponges increased the number of lung metastases in WT mice but not in corresponding Nox2-/- mice. Moreover, treatment with the NOX2 inhibitor histamine dihydrochloride (HDC) significantly reduced the formation of metastases in inflamed WT mice. Blood was drawn from WT and Nox2-/- mice one week after the sponge implantation to determine the extent of the inflammatory response. In sponge-bearing WT mice, there was a significant increase in the frequency of Ly6C+ inflammatory monocytes (p<0.001, n=22) and in their formation of ROS (p<0.01, n=14). No increase in inflammatory monocytes was noted in sponge-bearing Nox2-/- mice (p>0.5, n=8). In vivo treatment with HDC completely prevented the increase in inflammatory monocytes in wounded WT mice (p<0.001, n=10). Additionally, we investigated the impact of inflammation on metastasis formed spontaneously from a solid tumor where we observed higher incidence of tumor outgrowth in sponge-bearing mice. These data suggest that surgical inflammation augments inflammatory monocyte levels in blood and their NOX2-derived ROS production, which may impair immunosurveillance and enhance metastasis.
dc.identifier.urihttps://hdl.handle.net/20.500.12380/256696
dc.language.isoeng
dc.setspec.uppsokLifeEarthScience
dc.subjectImmunologi
dc.subjectCell- och molekylärbiologi
dc.subjectImmunologi inom det medicinska området
dc.subjectLivsvetenskaper
dc.subjectImmunology
dc.subjectCell and Molecular Biology
dc.subjectImmunology in the medical area
dc.subjectLife Science
dc.titleThe Impact of Surgery-induced Inflammation on Anti-neoplastic Immunity and Metastasis
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster Thesisen
dc.type.uppsokH
local.programmeBioteknik 300 hp (civilingenjör)
Ladda ner
Samling
Examensarbeten för masterexamen