Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma - 13/09/23
, Xuefeng Kan a, b, ⁎ Abstract |
Background and aims |
Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC).
Approach and results |
The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8+ T cells in combination with an αPD-1 antibody on Hepa1–6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8+ T cells in combination with αPD-1 antibody significantly enhanced the function of CD8+ T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8+ T cells and significantly decreased the number of FoxP3+ regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups.
Conclusions |
The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs.
Availability of data and material |
The data of this study are available from the corresponding author on reasonable request.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
OK-432 in combination with anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC). The iRFA of HCC releases large amounts of tumor-specific antigen, which can be phagocytosed by DCs. OK-432 treatment can promote the maturation of DCs and subsequently induce an increased tumor infiltration of CD8+ T cells. Moreover, anti-PD-1 antibody treatment relieved the immunosuppression of CD8+ T cells by blocking the PD-1/PD-L1 signaling pathway and significantly increased the killing ability of CD8 + T cells against residual viable tumor cells after RFA of HCC.
OK-432 in combination with anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC). The iRFA of HCC releases large amounts of tumor-specific antigen, which can be phagocytosed by DCs. OK-432 treatment can promote the maturation of DCs and subsequently induce an increased tumor infiltration of CD8+ T cells. Moreover, anti-PD-1 antibody treatment relieved the immunosuppression of CD8+ T cells by blocking the PD-1/PD-L1 signaling pathway and significantly increased the killing ability of CD8 + T cells against residual viable tumor cells after RFA of HCC.ga1Le texte complet de cet article est disponible en PDF.
Highlights |
• | OK-432 promoted DCs maturation and antigen-presenting ability. |
• | OK-432 treatment increased conventional DC1 (cDC1) in tumor bed. |
• | OK-432 plus αPD-1 antibody resulted in an excellent synergistic anti-tumor effect. |
Keywords : Radiofrequency ablation, Hepatocellular carcinoma, OK-432, Programmed death-1
Plan
Vol 166
Article 115351- octobre 2023 Retour au numéro
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