Journal
ONCOLOGY LETTERS
Volume 23, Issue 2, Pages -Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2021.13161
Keywords
renal cell carcinoma; 4-1BB; immunostimulating factor; CD11c(+)CD8(+) T cells; IFN-gamma
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2017R1D1A1B03036287, NRF-2017R1D1A1B03032831, NRF-2014R1A6A1030318, NRF-2015R1D1A1A01059994]
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This study aimed to improve the treatment strategies for incurable renal cell carcinoma (RCC). The combination therapy of immunostimulatory factor (ISTF) and anti-4-1BB monoclonal antibodies (mAbs) was established to enhance the antitumor response in a murine RCC model. The results showed that this combination therapy promoted partial tumor regression by increasing the number of activated effector cytotoxic T lymphocytes and IFN-gamma production.
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-alpha, 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-gamma-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-gamma 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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