التفاصيل البيبلوغرافية
| العنوان: |
Data from Anti-CD137 Suppresses Tumor Growth by Blocking Reverse Signaling by CD137 Ligand |
| المؤلفون: |
Byungsuk Kwon, Hong R. Cho, Byoung S. Kwon, Su K. Seo, Hyeon-Woo Lee, Hyeon H. Kim, Juyang Kim, So H. Park, Sang C. Lee, Sang W. Kang |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
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. |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::476127927b5c7cc2406b99ffce35f70d
https://doi.org/10.1158/0008-5472.c.6510197 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....476127927b5c7cc2406b99ffce35f70d |
| قاعدة البيانات: |
OpenAIRE |
