Multiple mechanisms have been raised: oncogenic signaling activation [11], upregulation of alternative immune checkpoints [12], major immune reactions caused by PD1/PDL1 inhibitors, previous irradiation [8], tumor proliferation via a direct (DNA damage with free radicals) or indirect (angiogenesis and tissue remodeling promotion) effect [13–15], expansion of PD1-expressing T-regulatory cells and modulation of tumour-promoting cells [16]. The gene discussed is CD274; the disease is neoplasm.