Parasite-enhanced immunotherapy: transforming the "cold" tumors to "hot" battlefields

Immunotherapy has emerged as a highly effective treatment for various tumors. However, the variable response rates associated with current immunotherapies often restrict their beneficial impact on a subset of patients. Therefore, more effective treatment approaches that can broaden the scope of therapeutic benefits to a larger patient population are urgently needed. Studies have shown that some parasites and their products, for example, Plasmodium, Toxoplasma, Trypanosoma, and Echinococcus, can effectively transform "cold" tumors into "hot" battlefields and reshape the tumor microenvironment, thereby stimulating innate and adaptive antitumor immune responses. These parasitic infections not only achieve the functional reversal of innate immune cells, such as neutrophils, macrophages, myeloid-derived suppressor cells, regulatory T cells, and dendritic cells, in tumors but also successfully activate CD4⁺/CD8⁺ T cells and even B cells to produce antibodies, ultimately resulting in an antitumor-specific immune response and antibody-dependent cellular cytotoxicity. Animal studies have confirmed these findings. This review discusses the abovementioned content and the challenges faced in the future clinical application of antitumor treatment strategies based on parasitic infections. With the potential of these parasites and their byproducts to function as anticancer agents, we anticipate that further investigations in this field could yield significant advancements in cancer treatment.