Immune checkpoint blockade (ICB) shows remarkable clinical effects in patients with
metastatic microsatellite-unstable (MSI) cancer. However, markers identifying potential
non-responders are missing. We examined the prevalence of Beta-2-microglobulin (B2M)
mutations, a common immune evasion mechanism, in stage IV MSI gastrointestinal
cancer and its influence on metastatic pattern and patients’ survival under ICB. Twentyfive
patients with metastatic, MSI gastrointestinal adenocarcinoma were included.
Eighteen patients received ICB with pembrolizumab and one patient with nivolumab/
ipilimumab. Sequencing was performed to determine B2M mutation status. B2M
mutations and loss of B2M expression were detected in 6 out of 25 stage IV MSI
cancers. B2M mutations were strongly associated with exclusively peritoneal/peritoneal
and lymph node metastases (p=0.0055). However, no significant differences in therapy
response (25% vs. 46.6%, p>0.99) and survival (median PFS: 19.5 vs 33.0 months,
p=0.74; median OS 39 months vs. not reached, p>0.99) were observed between B2Mmutant
and B2M-wild type tumor patients. Among metastatic MSI GI cancers, B2Mmutant
tumors represent a biologically distinct disease with distinct metastatic patterns.
To assess ICB response in B2M-mutant MSI cancer patients, future studies need to
account for the fact that baseline survival of patients with B2M-mutant MSI cancer may be
longer than of patients with B2M-wild type MSI cancer.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84360 |
| Date | 28 March 2023 |
| Creators | Busch, Elena, Ahadova, Aysel, Kosmalla, Kosima, Bohaumilitzky, Lena, Pfuderer, Pauline L., Ballhausen, Alexej, Witt, Johannes, Wittemann, Jan-Niklas, Bläker, Hendrik, Holinski-Feder, Elke, Jäger, Dirk, von Knebel Doeberitz, Magnus, Haag, Georg Martin, Kloor, Matthias |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2234-943X, 669774 |
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