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

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.

Automated summary

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.