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MSS CRC ICI Resistance — SCE Medical Oncology MCQ

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ModerateGI CancersMSS CRC ICI ResistanceSCE Medical Oncology

A 55-year-old woman with metastatic CRC has molecular profiling showing microsatellite stable (MSS) disease with a tumour mutational burden of 3 mutations per megabase. She asks whether immunotherapy will work for her. What is the expected ICI response rate in MSS CRC?

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Correct answer: D — Approximately 0-5% — MSS CRC is generally immunotherapy-resistant; standard chemotherapy ± targeted therapy remains the backbone; combination ICI strategies for MSS CRC are being investigated in clinical trials

MSS CRC (~85% of all CRC) is an 'immunologically cold' tumour with low TMB, limited neoantigen presentation and an immunosuppressive TME. Single-agent anti-PD-1 response rates are ~0-5%. This contrasts with MSI-H CRC (~40-50% ORR). Combination strategies (ICI + anti-VEGF, ICI + MEK inhibitors, ICI + radiotherapy) are being evaluated to convert 'cold' MSS tumours to 'hot'. Currently, no ICI approach is standard for MSS mCRC.

Reference: ESMO 2024 mCRC; KEYNOTE-177