English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Programmed cell death-1 (PD-1) has demonstrated impressive clinical outcomes in several malignancies, but its therapeutic efficacy in the majority of colorectal cancers is still low. Therefore, methods to improve its therapeutic efficacy in colorectal cancer (CRC) patients need further investigation. Here, we demonstrate that immunogenic chemotherapeutic agents trigger the induction of tumor PD-L1 expression in vitro and in vivo, a fact which was validated in metastatic CRC patients who received preoperatively neoadjuvant chemotherapy (neoCT) treatment, suggesting that tumor PD-L1 upregulation by chemotherapeutic regimen is more feasible via PD-1/PD-L1 immunotherapy. However, we found that the epigenetic control of tumor PD-L1 via DNA methyltransferase 1 (DNMT1) significantly influenced the response to chemotherapy. We demonstrate that decitabine (DAC) induces DNA hypomethylation, which not only directly enhances tumor PD-L1 expression but also increases the expression of immune-related genes and intratumoral T cell infiltration in vitro and in vivo. DAC was found to profoundly enhance the therapeutic efficacy of PD-L1 immunotherapy to inhibit tumor growth and prolong survival in vivo. Therefore, it can be seen that DAC remodels the tumor microenvironment to improve the effect of PD-L1 immunotherapy by directly triggering tumor PD-L1 expression and eliciting stronger anti-cancer immune responses, providing potential clinical benefits to CRC patients in the future.

Decitabine Augments Chemotherapy-Induced PD-L1 Upregulation for PD-L1 Blockade in Colorectal Cancer