Overexpressed PseudogeneHLA-DPB2Promotes Tumor Immune Infiltrates by RegulatingHLA-DPB1and Indicates a Better Prognosis in Breast Cancer

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 pseudogeneHLA-DPB2and its parental geneHLA-DPB1were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed thatHLA-DPB2might serve as an endogenous RNA to increaseHLA-DPB1expression by competitively binding withhas-miR-370-3p. Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that theHLA-DPB2/HLA-DPB1axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of theHLA-DPB2andHLA-DPB1were 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 thatHLA-DPB2can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, theHLA-DPB2andHLA-DPB1expression 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 pseudogeneHLA-DPB2can upregulateHLA-DPB1through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting theHLA-DPB2/HLA-DPB1axis with ICIs may optimize the current immunotherapy for BC.