Abstract
With immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy emerging as the fourth pillar of cancer treatment, modern oncology has entered a new era. However, clinical challenges-including primary/secondary resistance, limited response rates (particularly in "cold tumors"), and potentially severe immune-related adverse events (irAEs)-significantly constrain their applicability and patient benefit. Traditional Chinese medicine (TCM), grounded in its holistic principles of tonifying the body's resistance while eliminating pathogenic factors and syndrome differentiation, demonstrates unique scientific value and translational potential through multi-component, multi-target synergistic actions. It remodels the tumor immune microenvironment (TME), enhances antitumor immune responses, and mitigates immunotherapy-related toxicities. This review systematically synthesizes current evidence elucidating core mechanisms by which TCM formulas, single compounds, and bioactive components enhance efficacy and reduce toxicity. Regarding efficacy enhancement, we focus on TCM's role in reversing T-cell exhaustion, reprogramming tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), inducing immunogenic cell death (ICD), modulating tumor metabolic reprogramming, and optimizing gut microbiota composition to potentiate systemic antitumor immunity. For toxicity reduction, we comprehensively synthesize clinical evidence and pharmacological mechanisms underlying TCM's mitigation of immune-related pneumonitis, colitis, cardiotoxicity, dermatotoxicity, and myelosuppression. This work establishes a robust theoretical foundation and scientific evidence for novel TCM-integrated strategies in cancer immunotherapy, while outlining future directions in the era of precision medicine.