Tumor Immunotherapy Progress: Arsenic Trioxide and Bee Venom from a Traditional Chinese Medicine Perspective

Abstract

Tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs), has become a cornerstone of comprehensive cancer treatment. Nevertheless, primary and acquired resistance remain persistent challenges in solid tumors, largely driven by an immunosuppre ssive tumor microenvironment (TME) and insufficient tumor immunogenicity. The traditional Chinese medicine (TCM) philosophy of Fuzheng Quxie — strengthening the body's vital qi while eliminating pathogenic factors —offers a compelling conceptual foundation for modulating the TME and converting immunologically “cold” tumors into “hot” ones. From the perspective of cellular stress and immune activation, this review systematically examines the immunomodulatory mechanisms and recent therapeutic advances of two rep resentative TCM-derived agents. We highlight how arsenic trioxide (ATO), beyond its classical success in acute promyelocytic leukemia (APL), triggers a “viral mimicry” effect by pharmacologically rescuing mutant p53, thereby potentiating systemic antitumor immunity via the cGAS -STING pathway. We also examine how melittin, the principal active component of bee venom, induces immunogenic cell death (ICD) and serves as a potent adjuvant in biomimetic nanovaccines for dendritic cell cross -presentation. Furtherm ore, emerging clinical evidence suggests that specific TCM formulae may extend this paradigm, improving response rates and mitigating immune -related toxicities when combined with ICIs. Looking forward, the integration of single -cell multi-omics, advanced nanodelivery systems, and biomarker -driven clinical trials is expected to transform TCM -assisted immunotherapy from empirical practice into evidence-based precision medicine.