Key points
- Every patient with bowel cancer should have the tumour's MMR or MSI status tested; the test is done on the same biopsy or surgical sample [1, 10].
- In MSI-H disease that has spread, immunotherapy controlled the disease about twice as long as chemotherapy, with a third of the serious side effects [2].
- Two immunotherapy drugs together had kept the disease quiet in most patients two years later; with chemotherapy, in only a few [4].
- Before and after surgery too, immunotherapy has had unprecedented results in these tumours [6, 7, 8].
What do MSI-H and dMMR mean?
Every time cells divide they copy their DNA, and an "error-correction system" (MMR) fixes copying mistakes. In some bowel tumours this system is broken (dMMR); the result is thousands of mutations in the tumour, which show up on testing as "high microsatellite instability" (MSI-H). These mutations make the tumour look "more foreign" to the immune system; that is why immunotherapy works very well in them (immunotherapy and organ preservation).
Sometimes this fault is inherited (Lynch syndrome), and family testing is also needed [10] (is cancer hereditary?).
The story: when chemotherapy stepped aside
For years, the treatment of bowel cancer that had spread was, for every patient, chemotherapy with targeted drugs. Then a large study compared immunotherapy with pembrolizumab directly with chemotherapy in MSI-H patients: the disease got worse about twice as late, and serious side effects were a third of those with chemotherapy [2]. In those who responded, the response usually lasted for years [3].
A combination of two immunotherapy drugs (nivolumab and ipilimumab) went a step further: two years later the disease had stayed quiet in most patients; with chemotherapy, in only a few [4]. This combination was also better than nivolumab alone [5].
Before and after surgery
Colon cancer: a few weeks of immunotherapy before surgery destroyed the tumour completely in the surgical specimen in 68 of 100 patients [6]. After surgery for stage 3 disease, adding immunotherapy to chemotherapy roughly halved relapses [7].
Rectal cancer: in one study, 6 months of immunotherapy destroyed the tumour in every patient, without the need for radiotherapy or surgery [8], and in a larger report most patients also avoided surgery [9]. This approach still needs longer follow-up and an experienced centre.
When should I call my doctor?
During immunotherapy, report diarrhoea or blood in the stool, a new cough or breathlessness, yellowing of the skin, severe tiredness or a widespread rash early; these may be immune-related inflammation that needs early treatment (side effects of immunotherapy).
Frequently asked questions
What percentage of bowel cancers are MSI-H?
Does immunotherapy help every bowel cancer?
No. In tumours with working MMR (most patients), immunotherapy alone usually does not work, and chemotherapy with targeted drugs is the main treatment [1].
For physicians
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MMR (IHC) or MSI testing in every colorectal cancer [10, 1]. KEYNOTE-177: median PFS 16.5 versus 8.2 months (HR 0.60), grade ≥3 adverse events 22% versus 66% [2]; final OS HR 0.74 with 60% crossover [3]. CheckMate 8HW: nivolumab + ipilimumab first line, 24-month PFS 72% versus 14% (HR 0.21) [4]; versus nivolumab alone HR 0.62 [5]. NICHE-2: pCR 68%, pathological response 98% [6]. ATOMIC: atezolizumab + mFOLFOX6 in dMMR stage III, 3-year DFS 86.3% versus 76.2% (HR 0.50) [7]. Dostarlimab in dMMR rectal cancer: cCR 12 of 12 [8]; 49 of 49 in the rectal cohort [9]. Doses: pembrolizumab in MSI-H.
Scientific evidence
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Scientific evidence
8 itemsPembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study
Atezolizumab plus FOLFOX for Stage III Mismatch Repair-Deficient Colon Cancer
Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer
Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial
Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer
Nonoperative Management of Mismatch Repair-Deficient Tumors
Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer
PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer
Read more
Related cancer types
References
10 referencesShow all references, 10 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study
- 4
- 5Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial
- 6
- 7
- 8
- 9Nonoperative Management of Mismatch Repair–Deficient Tumors
- 10
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
Printed from the website; the full and up-to-date version: https://drdabiri.com/en/articles/msi-high-colorectal-cancer-immunotherapy/
