DNA Methylation of Immune Checkpoints in the Peripheral Blood of Breast and Colorectal Cancer Patients

The immune checkpoints (ICs) discovery has shifted the research into a new era, through which we no longer fully depend on chemotherapy and radiotherapy. Instead, we target our own immune cells to tackle cancer. However, aberrant expression of ICs prompts an immunosuppressive microenvironment that supports immune evasion of tumor cells. In this study, we investigated the transcriptomic expression and promoter DNA methylation status of different ICs/ligand including PD-1, CTLA-4, LAG-3, TIM-3, TIGIT and PD-L1 in peripheral blood of primary breast cancer (PBC) and colorectal cancer (CRC) patients, compared to healthy donors (HD). We found that ICs/PD-L1 were upregulated, except LAG-3, in the peripheral blood of PBC and CRC patients. Furthermore, we found that the promoter DNA methylation status of TIGIT in CRC and PD-L1 in PBC and CRC patients were hypomethylated, compared to HDs. This study is the first to disclose that the upregulation of TIGIT and PD-L1 in the circulation could be under the control of DNA methylation in the promoter regions. The more the hypomethylation, the higher the expression. These data indicate that the underlying mechanisms behind peripheral upregulation of PD-L1 and TIGIT in cancer patients could be due to aberrant promoter methylation status. These finding could have important implications for future prognosis and/or therapeutic purposes in these two common cancers.