Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10

• DOI: 10.1016/j.phrs.2023.106988
• Publication Date: 2023-11-19T17:29:41Z
• Authors: Mu-Yang Huang; Yu-Chi Chen; Wen-Yu Lyu; Xin-Yu He; Zi-Han Ye; Can-Yu Huang; Xin-Ling He; Xiuping Chen; Xiaobing Chen; Baoxian Zhang; Guoyin Kai; Xiaolei Zhang; Ting Li; Mingqing Huang; Jin-Jian Lu
• Keywords: Cancer Immunotherapy; CXCR3; Infiltration (HVAC)

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, anti-PD-1/PD-L1 antibodies only achieve response rate approximately 20%. Herein, we identified novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved anti-cancer efficacy anti-PD-L1 antibody in mice bearing MC38 tumor. combined with (combo treatment) further triggered infiltration, proliferation activation CD8+ T cells tumor microenvironment (TME). Depletion by mouse CD8 blocking abolished effect combo treatment totally. Mechanistically, increased expression CXCL10 through activating TBK1-IRF3 signaling pathway, explaining infiltration cells. Employing anti- CXC chemokine receptor 3 (CXCR3) prevented treatment. Meanwhile, percentage M1-like macrophages raised ratio M1/M2 TME. By comparing among MC38, CT26 4T1 tumors, resident were considered prerequisite for effectiveness These findings demonstrated potentiated PD-L1 via promoting activation, which shed new light on to enhance immunotherapy using natural product Rh2.