The microbial revolution: Akkermansia muciniphila's role in overcoming immunotherapy challenges

As research on tumor immune microenvironment (TIME) has deepened, immune checkpoint inhibitors (ICIs) have contributed to fundamental changes in the treatment of various cancers recently. As an immune checkpoint molecule, programmed cell death protein 1 (PD-1) is instrumental in dampening immune reactions and fostering tolerance. Accordingly, programmed cell death ligand 1 (PD-L1) resulted in tumor immune evasion by engaging with PD-1, potentially leading to the therapeutic failure. Although directed against the PD-1/PD-L1 pathway through immunotherapy has seen remarkable progress in treating multiple cancers, it also presents substantial challenges including a low remission rate to be addressed. In many cases, the anti-PD-1/PD-L1 therapy is not an exclusive approach constraining anticancer immunity, and simply inhibiting this axis may not be adequate to elicit a potent antitumor immune reaction, making the combined therapy a potentially superior approach. Countless research has indicated pronounced changes in gut microbiota as various diseases, particularly cancers. Currently, Akkermansia muciniphila (Akk), a representative commensal bacterium of potential next-generation probiotics (NGPs), has received substantial attention. The ingredients and metabolites of Akk can either immediately or indirectly modulate the cancer genesis, predominantly by fortifying the antitumor immune surveillance, which translates into more positive outcomes covering the cancer aversion and alleviation. In this paper, we comprehensively synthesis the anticancer mechanisms and defects of PD-1/PD-L1 blockers. Least of all, we carefully discuss the role of Akk in diverse tumorigenesis and the correlation with anti-PD-1/PD-L1 therapy. Likewise, we also demonstrate major scientific hurdles awaiting resolution for the prospective application of Akk as a beneficial bacterium for oncologic treatment functioning with PD-1/PD-L1 inhibitors, which could furnish illuminating guidance and support for the implementation of Akk-targeting medications within oncological therapies.