Exploration of Epigenetic Concepts That Impact Cancer Immune Infiltration and Immunotherapy
A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".
Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 4742
Special Issue Editor
Interests: cancer genomics and epigenomics; cancer biomarker discovery; cancer drug resistance; predictive cancer biology; immuno-oncogenomics; cancer metastasis; early cancer detection
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Immune checkpoint inhibitors (ICI) have been a remarkable addition to the fast-expanding group of cancer treatment options. Drugs targeting CTLA4 (ipilimumab), PD-1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), and PD-L1 (atezolizumab, avelumab, and durvalumab) have been approved for the treatment of a wide range of cancers. However, the accumulated clinical and research data have revealed that the effectiveness of ICIs can be limited by factors inherent to the biology of the tumors and their microenvironment. For example, the extent and type of tumor-infiltrating lymphocytes (TIL) surrounding cancer cells may determine if the patient will benefit from the treatment. To date, ICIs have been approved to treat cancers such as metastatic melanoma and MSI-high colorectal cancer, which generally exhibit high levels of TIL. The eventual aim is for ICI (and other forms of immunotherapy) to be a more cost-effective option against earlier-stage cancers. This possibility hinges on a deeper understanding of the biology of the interaction between cancer and immune cells and the associated immune toxicity of ICIs. It also necessitates identifying and testing new immunotherapeutic targets and the development of diagnostic assays (including non-invasive tools) that can accurately stratify patients based on predicted response to ICI therapy. The epigenetic regulatory processes play crucial roles in the interaction between immune and cancer cells. Integrated analyses of public genomic, epigenomic, and protein–DNA interaction datasets would indicate that the transcription of many immune-related genes, such as T cell receptor genes (e.g., CD3D), PRF1, GZMA, and the ICI targets CTLA4 and PDCD1, is highly regulated at the epigenetic level. In addition, several recent studies suggest that specific methylation markers in cancer tissues can be surrogate markers for TILs and T cell cytotoxic activity. The CpG methylation-driven repression of mismatch repair genes can lead to an elevated mutational burden, and, in turn, effecting the immunogenicity of tumor cells. Finally, given the importance of epigenetic processes in regulating immune processes, it would also be interesting to examine how epigenetic drugs (i.e., those targeting DNA methyltransferases, histone deacetylases, and bromodomain-containing proteins), as well as nutrition (which may also influence epigenetic processes), may modulate ICI. This convergence of cancer biology, therapeutics, epigenetics, immunology, and perhaps nutrition is genuinely fascinating. Authors interested in this field (basic, translational, or clinical) are welcome to contribute reviews or original research articles.
Dr. Manny D. Bacolod
Guest Editor
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Keywords
- immunotherapy
- epigenetics
- methylation
- microenvironment
- immune checkpoint inhibitor
- CTLA4
- PDL1
- PD1
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