# Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)

Source: https://onco.cc/terms/mss-pmmr/  
OnCo record `mss-pmmr` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The 'normal' result on the mismatch-repair test: the tumour has intact DNA spell-checking and few mutations. It describes about 95% of metastatic colorectal cancers and means checkpoint inhibitors alone are unlikely to work.

## Summary

The opposite of MSI-high/dMMR. MSS tumours have low mutational burden and few neoantigens, so PD-1 blockade produced almost no responses in colorectal cancer (KEYNOTE-016), and the immunotherapy revolution in dMMR colorectal and endometrial cancer (CheckMate 8HW, dostarlimab) has bypassed them. Making MSS colorectal cancer immune-responsive with combinations (botensilimab-balstilimab, KRAS inhibitors plus PD-1, cancer vaccines) is one of the field's biggest open problems. In endometrial cancer pMMR patients benefit less from adding immunotherapy to chemotherapy but still gain (RUBY, NRG-GY018).

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: MSS; pMMR; microsatellite-stable; microsatellite stable; mismatch repair proficient; mismatch-repair proficient; MMR-proficient; MMR proficient; MSI-low; MSS/pMMR

## Notes

- Why this group resists immunotherapy, and what is being done about it. Median tumour mutational burden is 5.7 per megabase against 56.9 in MSI-high disease (cBioPortal crc_msk_2026), but low mutation load is not the whole reason: mice carrying all four main colorectal mutations reproduce the human microsatellite-stable phenotype with T-cell exclusion and TGF-beta-activated stroma, and blocking TGF-beta made their liver metastases susceptible to checkpoint blockade (Tauriello 2018), while tumour-cell WNT activation independently tracks the absence of T cells (Grasso 2018). The phase 3 test of atezolizumab with or without a MEK inhibitor failed against regorafenib (Eng 2019); the one credible signal is botensilimab plus balstilimab, 17% response in 101 evaluable patients (Bullock 2024).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Microsatellite_instability
- Wikipedia: https://en.wikipedia.org/wiki/Microsatellite_instability

## Connected records

- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Immuno-oncology (IO) and checkpoint blockade](https://onco.cc/terms/immuno-oncology/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- cancers: [Advanced or recurrent endometrial cancer](https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Endometrial cancer with no specific molecular profile](https://onco.cc/cancers/endometrial-nsmp/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- trials: [CheckMate 8HW](https://onco.cc/trials/checkmate-8hw/)
- key papers: [Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)](https://onco.cc/key-papers/paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019/), [Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial](https://onco.cc/key-papers/paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024/), [Deficient mismatch repair system in patients with sporadic advanced colorectal cancer](https://onco.cc/key-papers/paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009/), [Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ](https://onco.cc/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/), [Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies](https://onco.cc/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/), [Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer](https://onco.cc/key-papers/paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016/), [Stromal gene expression defines poor-prognosis subtypes in colorectal cancer](https://onco.cc/key-papers/paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015/), [TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis](https://onco.cc/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/)
- drugs: [VENTANA MMR RxDx Panel](https://onco.cc/drugs/ventana-mmr-rxdx/)
- technologies: [MSI and mismatch-repair testing](https://onco.cc/technologies/msi-mmr-testing/)
- targets: [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [POLE](https://onco.cc/targets/pole/)
- biomarkers: [MSI-high (microsatellite instability by PCR or sequencing)](https://onco.cc/biomarkers/msi-high/)

---
JSON: https://onco.cc/api/v1/entities/mss-pmmr.json