Mechanistically, PD-1/CD80 carried on immunocyte-derived sEVs (I-sEV) increases secretion of PD-L1+ sEVs into circulation and decreases membrane expression of PD-L1, as well as antigen presentation and intercellular adhesion molecules, on tumour cells, leading to an immunologically ‘cold’ phenotype. The gene discussed is PDCD1; the disease is neoplasm.