American Association for Cancer Research
00085472can202324-sup-247020_2_supp_6636796_qt3tl1.docx (393.59 kB)

Supplementary Figures S1 to S6 from RIG-I–Like Receptor LGP2 Is Required for Tumor Control by Radiotherapy

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journal contribution
posted on 2023-03-31, 04:01 authored by Wenxin Zheng, Diana Rose E. Ranoa, Xiaona Huang, Yuzhu Hou, Kaiting Yang, Elizabeth C. Poli, Michael A. Beckett, Yang-Xin Fu, Ralph R. Weichselbaum

Figure S1. describes the apoptotic status of tumor infiltrating and antigen specific CD8+ T cells; Figure S2. describes the apoptotic status and cell surface phenotype of BMDCs; Fig S3. shows an association analysis of LGP2 and overall survival of TNBC and Luminal A patients who received RT; Fig S4. shows correlation analysis between LGP2 expression and clinical outcome of melanoma and sarcoma patients; Figure S5. shows Correlation between gene expression level of LGP2 (DHX58) and signature genes of DCs and CD8+ T cells in human melanoma; Fig S6. shows an association between LGP2 expression and prognosis in pancreatic cancer and colorectal cancers.



Dendritic cells (DC) play an essential role in innate immunity and radiation-elicited immune responses. LGP2 is a RIG-I–like receptor involved in cytoplasmic RNA recognition and antiviral responses. Although LGP2 has also been linked to cell survival of both tumor cells and T cells, the role of LGP2 in mediating DC function and antitumor immunity elicited by radiotherapy remains unclear. Here, we report that tumor DCs are linked to the clinical outcome of patients with breast cancer who received radiotherapy, and the presence of DC correlates with gene expression of LGP2 in the tumor microenvironment. In preclinical models, host LGP2 was essential for optimal antitumor control by ionizing radiation (IR). The absence of LGP2 in DC dampened type I IFN production and the priming capacity of DC. In the absence of LGP2, MDA5-mediated activation of type I IFN signaling was abrogated. The MDA5/LGP2 agonist high molecular weight poly I:C improved the antitumor effect of IR. This study reveals a previously undefined role of LGP2 in host immunity and provides a new strategy to improve the efficacy of radiotherapy. These findings reveal an essential role of LGP2 in promoting antitumor immunity after radiotherapy and provide a new strategy to enhance radiotherapy.