Epigenetic factors driving immunological tolerance in cancer immunotherapy

Cancer immunotherapies targeting the CTLA-4 and the PD-1/PD-L1 axis, which activate T cells and promote anti-tumor immunity, are revolutionizing the treatment pattern for various cancer types. Nevertheless, despite the fact that such immunotherapies effectively enhance long-term response and permanent disease control, only a small proportion of patients can benefit from them. Most patients have primary or acquired resistance to cancer immunotherapy. Recent studies report that the response to cancer immunotherapy mainly depends on the dynamic interaction between tumor cells and tumor immune microenvironment (TIME). Among them, TIME is the internal environment for tumor cells to survive and develop and is also the "main battlefield" for immune cells to kill tumor cells. However, the therapeutic impact of immunotherapy is influenced by the interaction between TIME and malignant cells, which mediates the immune tolerance in cancer immunotherapy. Epigenetic alterations are well-acknowledged to be used by tumor cells to impair their immunogenicity and immune recognition. The expression of key molecules in tumor cells and the host immune system regulated directly or indirectly by epigenetic regulation can affect the identification of immune system or damage the activity of the immune system, thus driving the immunological tolerance in tumor immunology.

This research topic aims to provide a forum to advance research on the discovery of epigenetic factors driving immunological tolerance in tumor immunology, as well as the delineation of the molecular mechanisms by which the epigenetic marks regulate anti-tumor responses and influence the effect of cancer immunotherapy. We welcome the submission of original research and review articles that include epigenetic factors driving immunological tolerance in multi-omics studies, mechanisms of epigenetic modulation-induced immunological tolerance in experimental approaches, as well as technologies or discoveries in epigenetic drugs reverting immunological tolerance.

Areas of interest include but are not limited to the following aspects:

1. Novel epigenetic molecules and their mechanisms involved in immunological tolerance

2. Epigenetic mechanisms of immune escape in cancer

3. Role of epigenetic modulation in regulating the immunosuppressive tumor microenvironment

4. Role of epigenetic modulation in regulating the expression of immune checkpoints, such as CTLA4, PD-1, PD-L1 and so on

5. Development of epigenetic drugs reverting immunological tolerance

6. Development of epigenetic targeting therapies to increase efficacy of immunotherapies

7. Clinical trials testing the efficacy of epigenetic targeting immunotherapies and combination with other immunotherapies

8. Novel technologies to understand the roles of epigenetic modulation in cancer immunity and immunotherapy

Keywords: epigenetic molecules, immunological tolerance, immune escape, epigenetic modulation

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