Journal: Nature
This phase II NICHE study evaluated neoadjuvant immune checkpoint blockade (nivolumab plus ipilimumab) in 31 patients with early-stage mismatch repair-proficient (pMMR) colon cancer.
The treatment yielded a 26% response rate, including:
- Six major pathological responses
- One ongoing clinical complete response without surgery
Circulating tumor DNA (ctDNA) clearance correlated strongly with responders.
Notably, responses occurred despite low tumor mutational burden. Responders showed:
- Higher chromosomal instability scores
- Elevated proliferation signatures
- Increased TCF1 expression
Imaging mass cytometry revealed greater proliferative activity in both cancer and CD8+ T cells of responders.
These findings highlight potential biomarkers for selecting patients likely to benefit from neoadjuvant immune checkpoint blockade in pMMR colon cancer.