Chang et al. showed that anti-PD-1 therapy increased the antitumor efficacy of DC-TEX by restoring exhausted tumor antigen-specific CD8+ T cells in an orthotopic HCC mouse model. DC-TEX treatment increased the number of CD8+ T cells, activation-associated cytokines, and PD‑1+ CD8+ T cells, peaking at 72 h post treatment. Anti-PD-1 increased the proliferation and cytokine production of PD‑1+ CD8+ T cells maximally at 72 h in vitro. The combination of DC-TEX and anti-PD-1 showed superior antitumor response to HCC in mice when PD-1 Ab was administered 72 h (vs 24, 120, and 168 h) after DC-TEX, suggesting that the timing of PD-1 Ab administration impacts the antitumor effect.
Contributed by Shishir Pant
ABSTRACT: Hepatocellular carcinoma (HCC), a prevalent cause of cancer-related deaths, is insensitive to traditional treatments. At different time intervals, the combined antitumor effects of DC-TEX and the programmed death protein 1 (PD-1) antibody (Ab) have not been investigated. In this study, HCC models were established and treated at different time intervals with DC-TEX alone or in combination with PD-1 Ab. In addition, we developed an orthotopic HCC model in BALB/c nude mice and restored T cells. Results demonstrated that the PD-1 + CD8 + T-cell population also increased significantly after DC-TEX treatment, in addition to the increased number of CD8 + T cells. The number of CD8 + T cells increased 72 h after DC-TEX administration. Similar observations were made for PD-1 + CD8 + T cells. Subsequently, PD-1 Ab was administered in combination with DC-TEX at different time points (0, 24, 72, 96, 120, or 168 h). Surprisingly, the combination treatment demonstrated a strong antitumor effect, which was very prominent when PD-1 Ab was administered at 72 h. PD-1 Ab significantly reversed the proliferative ability of PD-1 + CD8 + T cells at 72 h in vitro. The combined antitumor effects of PD-1 Ab and DC-TEX occurred mainly by stimulating CD8 + T cell proliferation and inhibiting T cell exhaustion. In conclusion, our results indicate that the combination of DC-TEX and PD-1 Ab significantly inhibits tumor growth in a murine HCC model and that the timing of PD-1 Ab administration impacts the antitumor effect.
Author Info: (1) Department of Gastrointestinal Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, #440 Jiyan Road, Hu
Author Info: (1) Department of Gastrointestinal Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, #440 Jiyan Road, Huaiyin District, Jinan, 250117, Shandong, China. (2) Department of Infection Management, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. (3) Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin Key Laboratory of Biomaterial Research, Tianjin, 300192, China. (4) Department of Gastrointestinal Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, #440 Jiyan Road, Huaiyin District, Jinan, 250117, Shandong, China. (5) Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin Key Laboratory of Biomaterial Research, Tianjin, 300192, China. (6) Department of Gastrointestinal Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, #440 Jiyan Road, Huaiyin District, Jinan, 250117, Shandong, China. sfmshishengbin@126.com. Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin Key Laboratory of Biomaterial Research, Tianjin, 300192, China. sfmshishengbin@126.com.
