Oscar Tahuahua, Medical Oncology Fellow at the National Cancer Institute of Mexico, shared a post on X:
“One hidden tumor population can decide if immunotherapy works or fails.
In CRC.
A single clonal neoantigen – ~70% durable response vs ~10% without it.
dMMR tumors respond but still fail due to heterogeneity.
ICI clears immunogenic clones – low-immunogenic subclones survive, expand and drive progression.
Key insight:
- it’s the weakest dominant one that escapes the immune system.
- It’s not about having more neoantigens, one dominant weak clone is enough to drive resistance.
This is one reason why even dMMR patients can fail.
Clinically
- Early PR ~12 weeks – ~75% durable benefit.
- Early SD – ~80% ultimately progress.”
Title: Neoantigen evolution and response to checkpoint inhibitor immunotherapy in colorectal cancer
Authors: Alanna Sholokhova, Kamran Kaveh, Ivana Bozic
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