AI Article Synopsis
- * A study was conducted to see if increasing the MMRd fraction in MMR heterogeneous tumors could enhance immune surveillance and potentially work like an “endogenous cancer vaccine.”
- * By mixing MMRp and MMRd mouse CRC cells and treating tumors with 6-thioguanine, researchers found that a significant proportion (at least 50%) of MMRd cells led to effective tumor rejection, indicating that enhancing MMRd could increase the tumors' immunogenicity.
Article Abstract
Patients affected by colorectal cancer (CRC) with DNA mismatch repair deficiency (MMRd), often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. Interestingly, a subset of MMRp CRCs contains variable fractions of MMRd cells, but it is unknown how their presence impacts immune surveillance. We asked whether modulation of the MMRd fraction in MMR heterogeneous tumors acts as an endogenous cancer vaccine by promoting immune surveillance. To test this hypothesis, we use isogenic MMRp (Mlh1) and MMRd (Mlh1) mouse CRC cells. MMRp/MMRd cells mixed at different ratios are injected in immunocompetent mice and tumor rejection is observed when at least 50% of cells are MMRd. To enrich the MMRd fraction, MMRp/MMRd tumors are treated with 6-thioguanine, which leads to tumor rejection. These results suggest that genetic and pharmacological modulation of the DNA mismatch repair machinery potentiate the immunogenicity of MMR heterogeneous tumors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833846 | PMC |
| http://dx.doi.org/10.1016/j.ccell.2022.12.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!