UCSF

Background/aim

The majority of colorectal cancer (CRC) cases, which are microsatellite stable (MSS) and do not harbor mismatch repair deficiency/microsatellite instability, are resistant to immunotherapy. Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed.

Case report

We report three cases of MSS CRC with durable clinical benefit from immunotherapy with anti-PD-1 checkpoint inhibitors. Two cases bear a POLE P286R mutation, which has been associated with lack of immunotherapy response in MSS CRC. Two cases bear alterations in Ataxia-Telangiectasia Mutated (ATM) which may contribute to observed responses, including interaction with a co-administered intratumoral stimulator of interferon genes (STING) pathway agonist in one patient.

Conclusion

Novel DNA damage repair alterations, including mutations in ATM, can provide insight into additional mechanisms by which genomic alterations can sensitize MSS CRC to diverse immunotherapies.