Micropeptide UEIS attenuates cGAS-STING-type I IFN signalling to repress anti-tumour immunity

Selectively restoring tumour-induced immune deficiency within the tumour microenvironment is considered an ideal strategy for unleashing antitumour immunity without causing severe toxicity. Here, we describe an immunoregulatory micropeptide encoded by a long non-coding RNA (lncRNA) gene identified through comprehensive bioinformatic screening, which we designate as UEIS.

UEIS was found to be upregulated in tumour-associated macrophages (TAMs) and to drive macrophages toward a pro-tumorigenic phenotype, thereby inhibiting antitumour T-cell immunity. Mechanistically, the expression of UEIS is induced by cGAS-STING-type I interferon (IFN) signalling at a relatively late stage following tumoral DNA stimulation. Thus, we identify the endogenous existence of a lncRNA-encoded micropeptide and reveal its inhibitory effect on cGAS-STING-type I IFN signalling via a feedback loop in TAMs.