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After briefly 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 howPD-1 and PD-1 ligands are involved in a new form of in immunosuppression that represents anew approach to cancer therapy. Namely, tumor cells often kill cytotoxic T lymphocytesthrough PD-1 mechanisms – hence, PD-L1 inhibitors represent a new molecular mechanism ofcancer immunotherapy (Jobin C., Science, 2018, 359, 32-34). Recent translational clinicalresearch also revealed a substantial influence of gut microbiome on response to PD-1-basedcancer immunotherapy. The initial discovery was that cancer patients treated with antibiotics forvarious infections have diminished response to anti-PD-1 therapy. Comparing the fecalmicrobiota of responders to non-responders revealed increased abundance of Akkermansiamuciniphila, Faecalibacteria a Bifidobacteria in patients showing favorable outcomes toanti–PD-1 treatment. (Gopalakrishnan V et al. Science, 2018,359,97-103). Conclusions: 1.Recent studies revealed how inhibition of certain cell death (e.g., cytotoxic T cells) via PD-1leads to increased death of tumor cells. 2. The effectiveness of PD-1-based cancerimmunotherapy is greatly influenced by gut microbiome (e.g., firmicutes and clostridia havepositive, while bacteroidia exert negative effects). 3. Nevertheless, checkpoint inhibitors (viaPD-1, PD-L1) represent a new and effective cancer immunotherapy, even in metastaticmelanoma. 4. Thus, the discoverers of PD-1 a PD-L1 rightly shared the 2018 Nobel Prize inPhysiology or Medicine.

PROTECTION OF T-LYMPHOCYTES VIA PD-1 RECEPTOR: NEW MOLECULAR MECHANISM OF CANCER IMMUNOTHERAPY