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Dendritic cells(DCs) play a protective role in the antitumor immunity of most cancers, which can be divided into conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Most current studies are only based on either cDCs or pDCs for the study of the relationship between DCs and breast cancer prognosis, without combining the two together. We aimed to select new biomarkers from pDCs and cDCs. In this paper, the xCell algorithm was first used to calculate the cellular abundance of 64 types of immune cells and stromal cells in tumor samples from the TCGA database, and the high-abundance pDC group and cDC group were divided according to the results of a survival analysis. Then, we looked for the co-expressed gene module of highly infiltrating pDC and cDC patients with a weighted correlation network analysis (WGCNA) and screened out the hub genes, including RBBP5, HNRNPU, PEX19, TPR, and BCL9. Finally, we analyzed the biological functions of the hub genes, and the results showed that RBBP5, TPR, and BCL9 were significantly related to the immune cells and prognosis of patients, and RBBP5 and BCL9 were involved in responding to TCF-related instructions of the Wnt pathway. In addition, we also evaluated the response of pDCs and cDCs with different abundances to chemotherapy, and the results showed that the higher the abundance of pDCs and cDCs, the higher their sensitivity to drugs. This paper revealed new biomarkers related to DCs—among them, BCL9, TPR, and RBBP5 were proven to be closely related to dendritic cells in cancer. For the first time, this paper puts forward that HNRNPU and PEX19 are related to the prognosis of dendritic cells in cancer, which also provides new possibilities for finding new targets for breast cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28− senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28− senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy. [ABSTRACT FROM AUTHOR]