Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model

• Published in: Frontiers in immunology 2021-09, Vol.12, p.737076-737076
• Main Authors: Lee, Eun-Ji, Kim, Ji Hye, Kim, Tae In, Kim, Yeon-Ji, Pak, Malk Eun, Jeon, Chang Hyun, Park, Yeo Jin, Li, Wei, Kim, Young Soo, Choi, Jang-Gi, Chung, Hwan-Suck
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Antibodies, Monoclonal, Humanized - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; cancer immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CHO Cells; Coculture Techniques; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - immunology; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cricetulus; humanized PD-1 mice; Humans; Immune Checkpoint Inhibitors - pharmacology; Immunology; Jurkat Cells; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; PD-1; PD-L1; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Sanguisorba - chemistry; Sanguisorbae Radix; Signal Transduction; Tumor Burden; tumor-infiltrating CD8+ T cell
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.737076

Immune checkpoints such as programmed death-1 (PD-1) have been proven as antitumor targets by enhancing cytotoxic T cell activity. All immune checkpoint blockades are antibody therapeutics that have large size and high affinity, as well as known immune-related side effects and low responses. To overcome the limitation of antibody therapeutics, we have explored PD-1/PD-L1 (programmed death-ligand 1) blockades in traditional oriental medicine, which has a long history but has not yet studied PD-1/PD-L1 blockades. Sanguisorbae Radix extract (SRE) blocked PD-1 and PD-L1 binding in competitive ELISA. SRE effectively inhibited the PD-1/PD-L1 interaction, thereby improving T cell receptor (TCR) signaling and the NFAT-mediated luciferase activity of T cells. SRE treatment reduced tumor growth in the humanized PD-L1 MC38 cell allograft humanized PD-1 mouse model. Additionally, the combination of SRE and pembrolizumab (anti-PD-1 antibody) suppressed tumor growth and increased infiltrated cytotoxic T cells to a greater extent did either agent alone. This study showed that SRE alone has anticancer effects PD-1/PD-L1 blockade and that the combination therapy of SRE and pembrolizumab has enhanced immuno-oncologic effects.