Anti‑4‑1BB antibody‑based combination therapy augments antitumor immunity by enhancing CD11c+CD8+ T cells in renal cell carcinoma

Ju,Seong-A; Park,Sang-Min; Joe,Yeonsoo; Chung,Hun Taeg; An,Won G.; Kim,Byung-Sam

doi:10.3892/ol.2021.13161

Anti‑4‑1BB antibody‑based combination therapy augments antitumor immunity by enhancing CD11c+CD8+ T cells in renal cell carcinoma

Authors:
- Seong-A Ju
- Sang-Min Park
- Yeonsoo Joe
- Hun Taeg Chung
- Won G. An
- Byung-Sam Kim
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Affiliations: School of Biological Sciences, University of Ulsan, Ulsan 44610, Republic of Korea, CEFO Co., Ltd., Seoul 03150, Republic of Korea, Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam 50612, Republic of Korea
Published online on: December 6, 2021 https://doi.org/10.3892/ol.2021.13161
Article Number: 43
Copyright: © Ju et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To improve the potential treatment strategies of incurable renal cell carcinoma (RCC), which is highly resistant to chemotherapy and radiotherapy, the present study established a combination therapy with immunostimulatory factor (ISTF) and anti‑4‑1BB monoclonal antibodies (mAbs) to augment the antitumor response in a murine RCC model. ISTF isolated from Actinobacillus actinomycetemcomitans stimulates macrophages, dendritic cells and B cells to produce IL‑6, TNF‑α, nitric oxide and major histocompatibility complex class II expression. 4‑1BB (CD137) is expressed in activated immune cells, including activated T cells, and is a promising target for cancer immunotherapy. The administration of anti‑4‑1BB mAbs promoted antitumor immunity via enhancing CD11c⁺CD8⁺ T cells. The CD11c⁺CD8⁺ T cells were characterized by high killing activity and IFN‑γ‑producing ability, representing a phenotype of active effector cytotoxic T lymphocytes. The present study showed that combination therapy with ISTF and anti‑4‑1BB mAbs promoted partial tumor regression with established RCC, but monotherapy with ISTF or anti‑4‑1BB mAbs did not. These effects were speculated to be caused by the increase in CD11c⁺CD8⁺ T cells in the spleen and tumor, and IFN‑γ production. These insights into the effector mechanisms of the combination of ISTF and anti‑4‑1BB mAbs may be useful for targeting incurable RCC.

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