The imbalance of immune status in cancer microenvironment plays an important role in the development and progression of cancer. Immunotherapy based on this has become an important field of cancer research in recent years. Many studies on long noncoding RNA (lncRNA) in cancer have focus on its regulation in cancer development and metastasis. Recent studies have suggested that lncRNAs play crucial roles in different phases of cancer immunity, including antigen releasing, antigen presentation, immune activation, immune cells migration, infiltrating into cancer tissues, and killing cancer cells. The functional studies of lncRNAs in cancer immuntity revealed the complicated molecular mechanisms in cancer immunity from a new point of view, which may provide novel potential targets for cancer immunotherapies. Based on the classical cancer-immunity cycle theory, we review the recent studies on the functions and mechanisms of immune-related lncRNAs in different stages of cancer immunity, to summarize the relationship between lncRNAs, and cancer immunity and to provide a framework for further research.
Increasing evidence shows that the anti-tumor functions of tumor-infiltrating T lymphocytes (TILs) were inhibited significantly, but the underlying mechanisms remain not fully understood. In this study, we found that 14-3-3ζ expression was up-regulated in hepatocellular carcinoma (HCC) cells and in TILs. TILs with 14-3-3ζ high-expression (14-3-3ζhigh) exhibited impaired activation (CD69), proliferation (Ki67) and anti-tumor functions compared to 14-3-3ζ low expression (14-3-3ζlow) TILs. Flow cytometry assay showed that compared with 14-3-3ζlow CD8+T cells, 14-3-3ζhigh ones exhibited higher frequency of exhausted phenotypes as measured by inhibitory receptors such as PD-1, TIM-3, LAG3, and CTLA-4. 14-3-3ζ overexpression inhibited the activity and proliferation of peripheral blood CD3+ T cells, deviated the differentiation of naive T cells from effector T cells to regulatory T cells. Moreover, we found that 14-3-3ζ expression levels in TILs correlated positively with those in HCC cells. Naive T cells co-cultured with HCC cells or the visible components of culture medium of HCC cells exhibited increased 14-3-3ζ expression. Stochastic optical reconstruction microscopy (STORM) and confocal assay showed that 14-3-3ζ-containing exosomes derived from HCC cells could be swallowed by T cells, suggesting that 14-3-3ζ might be transmitted from HCC cells to TILs at least partially through exosomes. In conclusion, our study for the first time demonstrated that 14-3-3ζ is up-regulated in and inhibited the anti-tumor functions of tumor-infiltrating T cells in HCC microenvironment and that 14-3-3ζ might be transmitted from HCC cells to T cells at least partially through exosomes.
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