In:
Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-8)
Kurzfassung:
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. Twenty-five 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 & gt;0.99) and survival (median PFS: 19.5 vs 33.0 months, p=0.74; median OS 39 months vs . not reached, p & gt;0.99) were observed between B2M -mutant and B2M -wild type tumor patients. Among metastatic MSI GI cancers, B2M -mutant 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.
Materialart:
Online-Ressource
ISSN:
2234-943X
DOI:
10.3389/fonc.2021.669774
DOI:
10.3389/fonc.2021.669774.s001
Sprache:
Unbekannt
Verlag:
Frontiers Media SA
Publikationsdatum:
2021
ZDB Id:
2649216-7