CD40L gene therapy tilts the myeloid cell profile and promotes infiltration of activated T lymphocytes
2014 (English)In: Cancer Gene Therapy, ISSN 0929-1903, E-ISSN 1476-5500, Vol. 21, no 3, 95-102 p.Article in journal (Refereed) Published
CD40 ligand (CD40L) is a potent stimulator of tumor immunity via its activation of dendritic cells, which in turn initiate T-cell activation. However, T cells are inhibited by suppressive myeloid cells, which constitute an important part of immune evasion. We hypothesized that CD40L may revert the function of suppressive myeloid cells to generate a T-cell stimulatory environment, and this was investigated in the murine bladder cancer model MB49/C57BL/6. Upon intratumoral adenoviral CD40L (AdCD40L) gene therapy, the infiltration of CD11b(+)Gr-1(+) cells was significantly reduced, whereas activated T cells were increased. In vitro, CD40L-expressing MB49 cells tilted the myeloid subpopulations in favor of granulocytic CD11b(+)Gr-1(high) myeloid cells instead of monocytic CD11b(+)Gr-1(int/low) myeloid cells. Further, the level of macrophages in splenocyte co-cultures with MB49 cells was evaluated. In cultures with MB49 cells expressing CD40L, the overall level of macrophages was reduced and the remaining cells were differentiated into M1-like cells. Hence, these data support that CD40L tilts myeloid immune cell populations in favor of anti-tumor immunity (M1) instead of immunosuppression (CD11b(+)Gr-1(int/low) and M2), and this was accompanied by an increased level of activated T cells in the tumor tissue.
Place, publisher, year, edition, pages
2014. Vol. 21, no 3, 95-102 p.
AdCD40L, myeloid-suppressor cells, M1 macrophages MB49, tumor microenvironment, tumor immunology
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-223902DOI: 10.1038/cgt.2014.2ISI: 000333069600002OAI: oai:DiVA.org:uu-223902DiVA: diva2:715503
De två sista författarna delar sista författarskapet.2014-05-052014-04-282015-04-10Bibliographically approved