Efficacy of immunotherapy in ARID1A-mutant solid tumors: a single-center retrospective study
Background Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying pati...
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Published in | Discover. Oncology Vol. 15; no. 1; pp. 213 - 13 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
07.06.2024
Springer Nature B.V Springer |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying patients who may benefit from ICIs is currently a challenge.
Methods
47 tumor patients harboring
ARID1A
mutations were retrospectively studied. The genomic profiling data through next-generation sequencing (NGS) and relevant clinical information were collected and analyzed. Additionally, bioinformatics analysis of the expression of immune checkpoints and immune cell infiltration levels was conducted in
ARID1A
-mutant gastric cancer (GC).
Results
ARID1A
mutations frequently co-occur with mutations in DNA damage repair (DDR)-associated genes. Among the 35
ARID1A
-mutant patients who received immunotherapy, 27 were evaluable., with the objective response rate (ORR) was 48.15% (13/27), and the disease control rate (DCR) was 92.59% (25/27). Moreover, survival assays revealed that
ARID1A
-mutant patients had longer median overall survival (mOS) after immunotherapy. In
ARID1A
-mutated GC patients, receiving ICIs treatment indicated longer progressive-free survival (PFS). Additionally, the incidence of microsatellite instability-high (MSI-H), high tumor mutation burden (TMB-H) and Epstein‒Barr virus (EBV) infection was elevated. Bioinformatic analysis showed significant enrichment of immune response and T cell activation pathway within differentially expressed genes in
ARID1A
-mutant GC group. Finally,
ARID1A
mutations status was considered to be highly correlated with the level of tumor infiltrating lymphocytes (TILs) and high expression of immune checkpoints.
Conclusions
Patients with tumors harboring
ARID1A
mutations may achieve better clinical outcomes from immunotherapy, especially in GC.
ARID1A
mutations can lead to genomic instability and reshape the tumor immune microenvironment (TIME), which can be used as a biomarker for immunotherapy. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2730-6011 2730-6011 |
DOI: | 10.1007/s12672-024-01074-1 |