{"entity":{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","aka":["MSS","pMMR","microsatellite-stable","microsatellite stable","mismatch repair proficient","mismatch-repair proficient","MMR-proficient","MMR proficient","MSI-low","MSS/pMMR"],"tldr":"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).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Microsatellite_instability","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Microsatellite_instability"}],"tags":[],"related":["msi","tmb","cold-vs-hot","immuno-oncology"],"cancers":["colorectal","endometrial"],"sections":["immunotherapy","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-8hw"],"people":[],"bottlenecks":[],"keyPapers":["paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015"],"journals":[],"dependsOn":[],"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)."],"category":"Biomarkers"},"route":"/terms/mss-pmmr/","neighbours":{"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"immuno-oncology","kind":"term","name":"Immuno-oncology (IO) and checkpoint blockade","route":"/terms/immuno-oncology/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"cancer":[{"id":"advanced-recurrent-endometrial-cancer","kind":"cancer","name":"Advanced or recurrent endometrial cancer","route":"/cancers/advanced-recurrent-endometrial-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"endometrial-nsmp","kind":"cancer","name":"Endometrial cancer with no specific molecular profile","route":"/cancers/endometrial-nsmp/"},{"id":"msi-high-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"trial":[{"id":"checkmate-8hw","kind":"trial","name":"CheckMate 8HW","route":"/trials/checkmate-8hw/"}],"paper":[{"id":"paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","kind":"paper","name":"Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)","route":"/key-papers/paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019/"},{"id":"paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","kind":"paper","name":"Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial","route":"/key-papers/paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024/"},{"id":"paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009","kind":"paper","name":"Deficient mismatch repair system in patients with sporadic advanced colorectal cancer","route":"/key-papers/paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009/"},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","route":"/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/"},{"id":"paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","kind":"paper","name":"Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies","route":"/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/"},{"id":"paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016","kind":"paper","name":"Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer","route":"/key-papers/paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016/"},{"id":"paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015","kind":"paper","name":"Stromal gene expression defines poor-prognosis subtypes in colorectal cancer","route":"/key-papers/paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015/"},{"id":"paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","kind":"paper","name":"TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis","route":"/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/"}],"drug":[{"id":"ventana-mmr-rxdx","kind":"drug","name":"VENTANA MMR RxDx Panel","route":"/drugs/ventana-mmr-rxdx/"}],"technology":[{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"pole","kind":"target","name":"POLE","route":"/targets/pole/"}],"biomarker":[{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"}]}}