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Immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma and non-small cell lung cancer. However, many patients with breast cancer (BC) show low response to ICIs due to the paucity of infiltrating immune cells. Pseudogenes, as a particular kind of long-chain noncoding RNA, play vital roles in tumorigenesis, but their potential roles in tumor immunology remain unclear. In this study that used data from online databases, the novel pseudogene  HLA-DPB2  and its parental gene  HLA-DPB1  were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that  HLA-DPB2  might serve as an endogenous RNA to increase  HLA-DPB1  expression by competitively binding with  has-miR-370-3p . Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the  HLA-DPB2/HLA-DPB1  axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the  HLA-DPB2  and  HLA-DPB1  were significantly associated with high immune infiltration abundance of CD8+ T cells, CD4+ T cells, Tfh, Th1, and NK cells and with high expression of majority biomarkers of monocytes, NK cell, T cell, CD8+ T cell, and Th1 in BC and its subtype, indicating that  HLA-DPB2  can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the  HLA-DPB2  and  HLA-DPB1  expression levels positively correlated with the expression levels of programmed cell death protein 1, programmed cell death ligand 1, and cytotoxic T-lymphocyte-associated antigen-4. Our findings suggest that pseudogene  HLA-DPB2  can upregulate  HLA-DPB1  through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting the  HLA-DPB2/HLA-DPB1  axis with ICIs may optimize the current immunotherapy for BC.

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer