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IL-1R8 expression in DLBCL regulates NK cell recruitment and influences patient prognosis

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Abstract 

The precise biological function of Interleukin-1 receptor 8 (IL-1R8) in diffuse large B-cell lymphoma (DLBCL) is still not well understood. Our goal is to decipher the profile of IL-1R8 expression status in DLBCL and to explore how IL-1R8 is involved in DLBCL progression. Utilizing a tissue microarray consisting of 70 samples of DLBCL tumors alongside 15 samples of tonsillitis, our investigation revealed a parallel expression profile of IL-1R8 between the tumor tissues and tonsillitis samples (p > 0.05). Nevertheless, an intriguing association emerged, as heightened expression of IL-1R8 correlated significantly with unfavorable survival outcomes in patients with DLBCL (p < 0.05). The status of IL-1R8 expression did not directly regulate proliferation (p > 0.05) and apoptosis (p > 0.05) in DLBCL cells via CCK8 and apoptotic assays. Subsequent chemotaxis analysis indicated that natural killer (NK) cell recruitment could be suppressed by IL-1R8 signaling in DLBCL, at least partially through CXCL1 inhibition (p < 0.05). The status of IL-1R8 expression in tumor tissues exhibited a negative correlation with the density of CD57+ NK cell infiltration (p < 0.05), while it did not demonstrate a significant association with CD3+ T cells (p > 0.05), CD68+ macrophages (p > 0.05), or S-100+ dendritic cells (p > 0.05). In line with this observation, elevated levels of NK cell infiltration demonstrated a significant positive correlation with improved overall survival (OS) among patients diagnosed with DLBCL (p < 0.05). Our data suggests the immuno-regulating potential of IL-1R8 through NK cell recruitment in DLBCL, providing novel insights into future immuno-modulating therapies.

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Data availability

The datasets generated for this study are available on request to the corresponding author.

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Funding

This study was supported by the National Natural Science Foundation of China (81960041, 81960043), the Natural Science Foundation of Jiangxi Province (20203BBGL73199) and the Science and Technology Innovation Foundation-Construction of the Clinical Medical Research Center (20211ZDG02006).

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Authors and Affiliations

  1. Department of Hematology, First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, Jiangxi, 330006, China

    Min Yu, Qian Zhang, Shixuan Wang, Lifang Zou, Zhiwei Chen & Fei Li

  2. Department of Oncology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

    Luying Wan

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  1. Min Yu
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  2. Qian Zhang
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  3. Luying Wan
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  4. Shixuan Wang
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  7. Fei Li
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Contributions

YM and ZQ designed the research and performed most analyses and experiments. WLY, WSX, ZLF and CZW assisted to analyze the patient’s clinical data. YM and ZQ drafted the manuscript and LF supervised the analysis. All authors contributed to the article and approved the submitted version.

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Correspondence to Fei Li.

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Yu, M., Zhang, Q., Wan, L. et al. IL-1R8 expression in DLBCL regulates NK cell recruitment and influences patient prognosis. Funct Integr Genomics 23, 328 (2023). https://doi.org/10.1007/s10142-023-01254-2

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