Abstract
After briefl y reviewing major forms of cell death and discovery of programmed (cell) death 1 (PD-1) protein and its ligands (PD-L1 and PD-L2), this overview is focused on how PD-1 and PD-1 ligands are involved in a new form of in immunosuppression that represents a new approach to cancer therapy. Namely, tumor cells often kill cytotoxic T lymphocytes through PD-1 mechanisms – hence, PD-L1 inhibitors represent a new molecular mechanism of cancer immunotherapy. Recent translational clinical research also revealed a substantial infl uence of gut microbiome on response to PD-1-based cancer immunotherapy. The initial discovery was that cancer patients treated with antibiotics for various infections have diminished response to anti-PD-1 therapy. Comparing the fecal microbiota of responders to non-responders revealed increased abundance of Akkermansia muciniphila, Faecalibacteria and Bifi dobacteria in patients showing favorable outcomes to anti–PD-1 treatment.
Conclusions: 1. Recent studies revealed how inhibition of certain cell death (e.g., cytotoxic T cells) via PD-1 leads to increased death of tumor cells. 2. The eff ectiveness of PD-1-based cancer immunotherapy is greatly infl uenced by gut microbiome (e.g., fi rmicutes and clostridia have positive, while bacteroidia exert negative eff ects). 3. Nevertheless, checkpoint inhibitors (via PD-1, PD-L1) represent a new and eff ective cancer immunotherapy, even in metastatic melanoma. 4. Thus, the discoverers of PD-1 and PD-L1 rightly shared the 2018 Nobel Prize in Physiology or Medicine.