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The generation of cancer-specific ribosomes by the lncRNA LISR suppresses melanoma anti-tumour immunity

ABSTRACT: Gains of chromosome 12p11.21, encoding for the cancer-specific lncRNA LISR, correlate with poor survival in the PanCancer Atlas. In melanoma, LISR is highly expressed by patients resistant to immunotherapy and it contributes to the generation of drug-tolerant persister cells by activating an immune suppressive translational program affecting the synthesis of PD-L1 and of the glycocalyx. Interestingly, the use of glycans to evade the immune system is a characteristic of the sperm. Accordingly, a defective glycocalyx assembly during spermatogenesis causes infertility. Here we show that LISR affects the core ribosome composition and recruits Deleted in AZoospermia Associated Protein 1 (DAZAP1) to regulate an immune suppressive translational program that includes PD-L1 and several glycosylases. Consequently, down-regulation of LISR leads to robust anti-tumour immune responses and re-sensitizes to immune checkpoint blockade. Our study reveals the contribution of lncRNAs to the generation of cancer-specific ribosomes and identifies an RNA-based cancer-specific strategy to overcome intrinsic resistance to immune checkpoint +blockade.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: alessandro cuomo

LAB HEAD: Eleonora Leucci

PROVIDER: PXD046528 | Pride | 2025-09-17

REPOSITORIES: Pride

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			Action	DRS
	HF181221_EL_Mito_PK_iST_01.raw	Raw
	HF181221_EL_Mito_iST_01.raw	Raw
	HF190115_EL_Mito_PK_iST_01.raw	Raw
	HF190115_EL_Mito_PK_iST_02.raw	Raw
	HF190115_EL_Mito_PK_iST_03.raw	Raw

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