Frontiers in Immunology (Oct 2022)

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

  • Yao Chen,
  • Yao Chen,
  • Anfu Zheng,
  • Anfu Zheng,
  • Anfu Zheng,
  • Yao Zhang,
  • Yao Zhang,
  • Yao Zhang,
  • Mintao Xiao,
  • Mintao Xiao,
  • Mintao Xiao,
  • Yueshui Zhao,
  • Yueshui Zhao,
  • Yueshui Zhao,
  • Xu Wu,
  • Xu Wu,
  • Xu Wu,
  • Mingxing Li,
  • Mingxing Li,
  • Mingxing Li,
  • Fukuan Du,
  • Fukuan Du,
  • Fukuan Du,
  • Yu Chen,
  • Yu Chen,
  • Yu Chen,
  • Meijuan Chen,
  • Meijuan Chen,
  • Meijuan Chen,
  • Wanping Li,
  • Wanping Li,
  • Wanping Li,
  • Xiaobing Li,
  • Xiaobing Li,
  • Xiaobing Li,
  • Yuhong Sun,
  • Yuhong Sun,
  • Yuhong Sun,
  • Li Gu,
  • Li Gu,
  • Li Gu,
  • Zhangang Xiao,
  • Zhangang Xiao,
  • Zhangang Xiao,
  • Jing Shen,
  • Jing Shen,
  • Jing Shen

DOI
https://doi.org/10.3389/fimmu.2022.1026076
Journal volume & issue
Vol. 13

Abstract

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BackgroundUveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear.MethodsData were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat.ResultsThe expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells.ConclusionsDysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.

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