American Association for Cancer Research
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Figure S2 from Anti-CD137 Suppresses Tumor Growth by Blocking Reverse Signaling by CD137 Ligand

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posted on 2023-03-31, 01:43 authored by Sang W. Kang, Sang C. Lee, So H. Park, Juyang Kim, Hyeon H. Kim, Hyeon-Woo Lee, Su K. Seo, Byoung S. Kwon, Hong R. Cho, Byungsuk Kwon

Figure S2. CD137-/- and anti-CD137-injected mice show enhanced antitumor immunity to EL-4 lymphoma and Renca renal carcinoma.

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Republic of Korea Ministry of Education

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ARTICLE ABSTRACT

CD137 (4-1BB) is a T-cell costimulatory molecule, and agonstic CD137 antibodies are currently being evaluated in the clinic as cancer immunotherapy. Recently, it was found that CD137−/− mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here, we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results. Specifically, CD137L suppressed intratumoral differentiation of IL12-producing CD103+ DC and type 1 tumor-associated macrophages (TAM). Differentiation of these cell types is important because they are required to generate IFNγ-producing CD8+ cytotoxic T lymphocytes (Tc1). Notably, CD137L blockade increased levels of IL12 and IFNγ, which promoted intratumoral differentiation of IFNγ-producing Tc1, IL12-producing CD103+ DC, and type 1 TAM within tumors. Our results offer an explanation for the paradoxical effects of CD137 blockade, based on differential immunomodulatory effects of CD137 signaling and reverse signaling in T cells and DC, respectively. Further, they show how CD137L blockade can seed a forward-feedback loop for activation of CD103+ DC/type 1 TAM and Tc1 that can create a self-perpetuating cycle of highly effective immunosurveillance. Cancer Res; 77(21); 5989–6000. ©2017 AACR.

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