Nat Commun: Chromatin accessability of circulating CD8-T cells predicts the response of gastric cancer patients to PD-1 therapy

Studies of immune cell failure and tumor-soaked lymphocyte (TIL) dysfunction caused by persistent antigen stimuli such as chronic viral infections and tumors have shown that cell surface proteins are associated with impaired immune cell function.
These proteins include multiple co-inhibitors or checkpoint subjects such as CTLA-4 (cytotoxic T lymphocyte antigen 4, CD152), PD-1 (programmed death subject 1, CD279), TIM-3 (T-cell immunoglobulin adhesive protein-3) and LAG-3 (lymphocyte active gene 3).
, clinical trials have been conducted using meso-antibodies (Abs) for immunosuppressant ICI to restore T-cell function.
these ICI drugs have now been approved for patients with metastatic stomach cancer (mGC) who have failed at least two systematic chemotherapy treatments.
although tumor genomic analysis has identified a small percentage of patients with stomach cancer (GC) who could benefit from anti-PD-1 treatment, not all reactions can be explained by tumor sequencing alone.
The molecular diagnostic schematic based on ATAC-seq explores the obitakous genetic factors associated with the response to differences in anti-PD-1 therapy by quantitatively assessing the accessability of whole genome chromatin to circulating CD8-T cells in the patient's outer blood.
Through atTIC-seq (a targeted open chromatin research method combined with high-volume sequencing techniques), the researchers identified a unique open area of chromatin that can distinguish between respondents and non-responders of anti-PD-1 therapy.
in the respondent group, GC patients with high chromatin openness of circulating CD8-T cells were significantly more developed.
correspondingly, patients with high chromosomal openness at specific genomic locations of circulating CD8-T cells had a significantly higher survival rate than those with chromosomal closure.
the correlation between
circulating CD8-T cell chromatin openness and anti-PD-1 therapy response, the study revealed that the ode genetic characteristics of baseline CD8-T cells could be used to identify metastasis GC patients who could potentially benefit from anti-PD-1 therapy.