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Updated: Oct 1, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Somatostatin Receptor 2: A Potential Predictive Biomarker for Immune Checkpoint Inhibitor Treatment
Aoyun Wang1,2, Yixiao Yuan3, Han Chu4
1Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Abstract:
Somatostatin receptor 2 (SSTR2), the most abundant receptor of somatostatin (SST), possesses immunoreactivity and is altered in many cancers. However, the association between SSTR2 and efficacy of immune checkpoint inhibitors (ICIs) has not yet been reported. Immunohistochemistry (IHC) information across 20 cancers was collected from the Human Protein Atlas (HPA) and used to analyze the expression of SSTR2. Immune signatures collected from public databases, such as BioCarta or Reactome, were used to investigate the association between SSTR2 and the tumor microenviroment in the Cancer Genome Atlas (TCGA). Data from cohorts treated with ICIs were collected to assess whether SSTR2 is associated with benefits from ICIs treatment. In the HPA, we found the SSTR2 IHC-positive rate of 13 cancers to be above 50%. Five types of cancer express SSTR2 mildly (positive rate: 25%-50%), while the remaining two types of cancer barely stained SSTR2-positive (positive rate: 0%-24%). In TCGA analysis, immune cell signatures and immune function pathways were enriched in high SSTR2 expression groups in most cancers. In each ICIs treated cohort, patients with high SSTR2 expression experienced numerically superior objective response rate (Braun: 14.8% vs 13.4%, p = 0.85; Gide: 69.4% vs 40.5%, p = 0.025; Mariathasan: 22.4% vs 16.7%, p = 0.233; Miao: 37.5% vs 11.8%; Riaz: 32.0% vs 7.7%, p = 0.067) and overall survival (Braun: HR (95%CI): 0.80 [0.62-1.04], p = 0.80; Gide: HR (95%CI): 0.61 [0.29-1.30], p = 0.20; Mariathasan: HR (95%CI): 0.83 [0.64-1.08], p = 0.16; Miao: HR (95%CI): 0.24 [0.086-0.65], p = 0.0028; Nathanson cohort: HR (95%CI): 0 [0-inf], p = 0.18; Riaz: HR (95%CI): 0.24 [0.086-0.65], p = 0.028) than patients with low SSTR2 expression. In pooled cohort, we found these differences were significant (Pool: 24.6% vs 16.7%, p = 0.0077; HR (95% CI): 0.77 [0.65-0.91], p = 0.0018). Our results suggest that SSTR2 is a potential predictive biomarker for response to ICIs.
Insights
Somatostatin receptor 2 (SSTR2) expression is linked to better outcomes with immune checkpoint inhibitors (ICIs). High SSTR2 levels correlate with improved response rates and survival in various cancers treated with ICIs.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Somatostatin receptor 2 (SSTR2) is highly expressed in many cancers and plays a role in tumor biology.
- The association between SSTR2 expression and the efficacy of immune checkpoint inhibitors (ICIs) remains largely unexplored.
Purpose of the Study:
- To investigate the expression of SSTR2 across various cancer types.
- To explore the relationship between SSTR2 expression and the tumor microenvironment.
- To determine if SSTR2 expression can predict patient response to ICIs.
Main Methods:
- Utilized immunohistochemistry data from the Human Protein Atlas (HPA) to assess SSTR2 expression in 20 cancer types.
- Analyzed immune signatures from The Cancer Genome Atlas (TCGA) to understand the link between SSTR2 and the tumor microenvironment.
- Collected and analyzed data from patient cohorts treated with ICIs to evaluate SSTR2's predictive value for treatment response and survival.
Main Results:
- SSTR2 was highly expressed (above 50% positive rate) in 13 of 20 analyzed cancers.
- Higher SSTR2 expression was associated with enriched immune cell signatures and immune function pathways in the tumor microenvironment.
- Patients with high SSTR2 expression showed numerically superior objective response rates and overall survival in multiple ICI-treated cohorts, with significant improvements observed in pooled analyses.
Conclusions:
- SSTR2 is frequently expressed in various cancers.
- SSTR2 expression is linked to a more immunogenic tumor microenvironment.
- SSTR2 represents a promising predictive biomarker for response to immune checkpoint inhibitor therapy.
