Long non-coding RNA prompts immune-related adverse events risk and immunotherapy response in pan-cancer
Abstract
Immune checkpoint inhibitors (ICIs) improve cancer outcomes but can cause immune-related adverse events (irAEs) that compromise treatment. Using FAERS real-world data, we developed a two-layer network algorithm to identify irAE-associated lncRNAs (irAEsLncs) across 18 cancer types. The irAEsLnc network showed organ-specific patterns and cancer-specific irAE susceptibility, while irAEsLncs were associated with immune infiltration, inflammatory responses, immune activation, and checkpoint molecules. Single-cell analysis of ICI-induced colitis linked irAEsLncs to inflammatory macrophage and T cell states and metabolic reprogramming. irAEsLnc-derived signatures independently predicted prognosis and responses to targeted therapy and immunotherapy, with ALAL-1/CD80/MEF2C predicting ICI efficacy in lung adenocarcinoma. Knockdown of ALAL-1 and SEC61G-DT suppressed tumor cell proliferation, migration, invasion, and macrophage-mediated inflammation. These findings connect irAE-associated lncRNAs with toxicity and antitumor immunity and support their potential as biomarkers for treatment stratification.
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BibTeX
@article{dong2026long,
title = {{Long non-coding RNA prompts immune-related adverse events risk and immunotherapy response in pan-cancer}},
author = {Longlong Dong and Lei Zhang and Lei Song and Changfan Qu and Xinyu Wang and Song Xiao and Miaomiao Tian and Peng Wang and Hui Zhi and Yanbin Zhao and Shangwei Ning and Yue Gao},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.118063},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03446-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Long non-coding RNA prompts immune-related adverse events risk and immunotherapy response in pan-cancer
AU - Longlong Dong
AU - Lei Zhang
AU - Lei Song
AU - Changfan Qu
AU - Xinyu Wang
AU - Song Xiao
AU - Miaomiao Tian
AU - Peng Wang
AU - Hui Zhi
AU - Yanbin Zhao
AU - Shangwei Ning
AU - Yue Gao
PY - 2026
DA - 2026/10/28
JO - iScience
DO - 10.1016/j.isci.2026.118063
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03446-2
AB - Immune checkpoint inhibitors (ICIs) improve cancer outcomes but can cause immune-related adverse events (irAEs) that compromise treatment. Using FAERS real-world data, we developed a two-layer network algorithm to identify irAE-associated lncRNAs (irAEsLncs) across 18 cancer types. The irAEsLnc network showed organ-specific patterns and cancer-specific irAE susceptibility, while irAEsLncs were associated with immune infiltration, inflammatory responses, immune activation, and checkpoint molecules. Single-cell analysis of ICI-induced colitis linked irAEsLncs to inflammatory macrophage and T cell states and metabolic reprogramming. irAEsLnc-derived signatures independently predicted prognosis and responses to targeted therapy and immunotherapy, with ALAL-1/CD80/MEF2C predicting ICI efficacy in lung adenocarcinoma. Knockdown of ALAL-1 and SEC61G-DT suppressed tumor cell proliferation, migration, invasion, and macrophage-mediated inflammation. These findings connect irAE-associated lncRNAs with toxicity and antitumor immunity and support their potential as biomarkers for treatment stratification.
SN - 2589-0042
ER -