Empowering cancer therapy: the promise of natural adjuvants

Cancer has consistently ranked as one of the major causes of mortality for numerous decades. Approximately 1 in 9 men and 1 in 12 women die from cancer-related deaths worldwide. Despite the development of numerous novel tactics and treatments, many of them have harmful side effects. As a result, there is a growing demand for products that are extracted or driven by natural processes as powerful anti-cancer agents due to their potential biological activities and various structural diversities; however, their chemical inertness and safety should be evaluated and standardized. Naturally extracted adjuvants are biologically derived substances that can enhance or modulate the immune response, including antigens, and may support cancer immunotherapeutic strategies. Furthermore, a natural adjuvant can promote the activation and maturation of the antigen-presenting cells (APCs), hence enhancing antigen presentation and processing linked to the major histocompatibility complex (MHC). Ultimately, stimulating the signaling pathways to regulate cytokine production and T-cell activation. Therefore, they are potential candidates in the management of cancers of the breast, melanoma, liver, and prostate, although there are variations in the supporting evidence among different subjects and cancer types. Depending on their formulations, natural adjuvants may be used as a component of drug or antigen-delivery systems, or can be incorporated into vaccine production. This review seeks to encapsulate the comprehensive activity of natural immunomodulators extracted from plants, microorganisms, and animals to exhibit adjuvant activity, and therefore emphasizes their immunological mechanisms and incorporation into cancer immunotherapy and related strategies.