Immunomodulation has emerged as a critical strategy in the fight against cancer. While synthetic immunotherapies, such as immune checkpoint inhibitors, micro and nanometric materials and engineered cytokines, have driven the advancement and application of innovative therapeutic approaches targeting cancer, the exploration of natural immunomodulators-derived from plants, microorganisms, and marine organisms-has also gained relevance. These agents can modulate immune responses by enhancing antigen presentation, activating cytotoxic lymphocytes, or introducing novel drug candidates and nanoparticle-based delivery systems. This evolving field bridges immunology, pharmacology, and oncology to develop novel agents that can overcome resistance mechanisms and improve patient outcomes. Understanding how both synthetic and natural compounds modulate immune pathways is essential for designing more effective and personalized cancer treatments.

Despite the remarkable progress of immunotherapy in oncology, many patients still experience limited responses or develop resistance. One of the major challenges lies in the complexity of tumor-immune interactions and the heterogeneity of immune responses across cancer types. Synthetic immunomodulators, such as checkpoint inhibitors, micro and nanometric materials, have shown efficacy, but their toxicity and limited effectiveness in certain cancers highlight the need for complementary strategies. Natural immunomodulators, derived from plants, fungi, and marine organisms, offer structurally diverse compounds with immunoregulatory potential and fewer side effects. However, their mechanisms of action remain underexplored, and standardization remains a barrier between the laboratory stage to clinical translation.

This Research Topic aims to address the current limitations by promoting studies that integrate synthetic and natural immunomodulatory approaches. We encourage submissions that explore combination of therapies, novel delivery systems, discovery of novel biomarkers, and new insights into immune activation or suppression mechanism. Manuscripts focusing on clinical relevance or therapeutic innovation are especially welcome. Through the integration of interdisciplinary research and highlighting recent advances, this Research Topic seeks to accelerate the development of more effective, safer, and personalized immunotherapies for cancer patients.

We welcome original research, reviews, mini-reviews, and brief research reports that address the following themes:

• Mechanisms of action of natural and synthetic immunomodulators in cancer
• Discovery and development of synthetic, nanoparticles, plant, marine, or microbe-derived immunomodulatory compounds
• Combination of strategies involving immunomodulators or other therapies
• Targeted delivery systems and nanotechnology-based approaches
• Development of innovative drug candidates and nanoparticle technologies for immune modulation
• Discovery of novel biomarkers for immunomodulatory response prediction to agents
• Repurposing of drugs and news including immunomodulators with cytotoxic activity on cancer cells or tumor
• Preclinical or translational models demonstrating efficacy or safety

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

Are you interested in contributing a manuscript to this Research Topic?

Natural and Synthetic Immunomodulators in Cancer