Abstract:
:Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with agonist anti-CD40 treatment confers superior antitumor efficacy and increased survival compared with monotherapy treatment in preclinical tumor models. Concurrent CSF-1R blockade and CD40 agonism lead to profound changes in the composition of immune infiltrates, causing an overall decrease in immunosuppressive cells and a shift toward a more inflammatory milieu. Anti-CD40/anti-CSF-1R-treated tumors contain decreased tumor-associated macrophages and Foxp3+ regulatory T cells. This combination approach increases maturation and differentiation of proinflammatory macrophages and dendritic cells and also drives potent priming of effector T cells in draining lymph nodes. As a result, tumor-infiltrating effector T cells exhibit improved responses to tumor antigen rechallenge. These studies show that combining therapeutic approaches may simultaneously remove inhibitory immune populations and sustain endogenous antitumor immune responses to successfully impair cancer progression. Cancer Immunol Res; 5(12); 1109-21. ©2017 AACR.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Wiehagen KR,Girgis NM,Yamada DH,Smith AA,Chan SR,Grewal IS,Quigley M,Verona RIdoi
10.1158/2326-6066.CIR-17-0258subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1109-1121issue
12eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-17-0258journal_volume
5pub_type
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