Related Experiment Video
Updated: Dec 12, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Tumor copy-number alterations predict response to immune-checkpoint-blockade in gastrointestinal cancer
Zhihao Lu1, Huan Chen2, Shuang Li1
1Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Background:
Despite the great achievements made in immune-checkpoint-blockade (ICB) in cancer therapy, there are no effective predictive biomarkers in gastrointestinal (GI) cancer.
Methods:
This study included 93 metastatic GI patients treated with ICBs. The first cohort comprising 73 GI cancer patients were randomly assigned into discovery (n=44) and validation (n=29) cohorts. Comprehensive genomic profiling was performed on all samples to determine tumor mutational burden (TMB) and copy-number alterations (CNAs). A subset of samples was collected for RNA immune oncology (IO) panel sequencing, microsatellite instability (MSI)/mismatch repair and program death ligand 1 (PD-L1) expression evaluation. In addition, 20 gastric cancer (GC) patients were recruited as the second validation cohort.
Results:
In the first cohort of 73 GI cancer patients, a lower burden of CNA was observed in patients with durable clinical benefit (DCB). In both the discovery (n=44) and validation (n=29) subsets, lower burden of CNA was associated with an improved clinical benefit and better overall survival (OS). Efficacy also correlated with a higher TMB. Of note, a combinatorial biomarker of TMB and CNA may better stratify DCB patients from ICB treatment, which was further confirmed in the second validation cohort of 20 GC patients. Finally, patients with lower burden of CNA revealed increased immune signatures in our cohort and The Cancer Genome Atlas data sets as well.
Conclusions:
Our results suggest that the burden of CNA may have superior predictive value compared with other signatures, including PD-L1, MSI and TMB. The joint biomarker of CNA burden and TMB may better stratify DCB patients, thereby providing a rational choice for GI patients treated with ICBs.
Insights
Copy number alterations (CNAs) and tumor mutational burden (TMB) can predict durable clinical benefit (DCB) from immune-checkpoint blockade (ICB) in gastrointestinal (GI) cancers. A combined biomarker of CNA burden and TMB offers improved patient stratification for ICB therapy.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Effective predictive biomarkers for immune-checkpoint blockade (ICB) are lacking in gastrointestinal (GI) cancers.
- Despite advancements, patient selection for ICB therapy remains a challenge in GI oncology.
Purpose of the Study:
- To identify reliable predictive biomarkers for durable clinical benefit (DCB) in metastatic GI cancer patients treated with ICB.
- To evaluate the predictive value of copy number alterations (CNAs) and tumor mutational burden (TMB) in this patient population.
Main Methods:
- Genomic profiling (TMB, CNAs) and RNA immune oncology panel sequencing were performed on 93 metastatic GI patients.
- Patients were divided into discovery (n=44) and validation (n=29) cohorts, with an additional validation cohort of 20 gastric cancer (GC) patients.
- Microsatellite instability (MSI) and program death ligand 1 (PD-L1) expression were also assessed.
Main Results:
- A lower burden of CNAs was associated with improved clinical benefit and overall survival (OS) in GI cancer patients treated with ICB.
- Higher TMB also correlated with efficacy.
- A combined biomarker of CNA burden and TMB demonstrated superior ability to stratify patients for DCB.
Conclusions:
- The burden of CNAs shows significant predictive value for ICB response in GI cancers, potentially outperforming PD-L1, MSI, and TMB alone.
- A joint biomarker incorporating CNA burden and TMB can enhance patient stratification for ICB therapy, guiding treatment decisions.
Related Concept Videos
01:27Tumor Immunotherapy
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...