A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma
Nan Sun1,2, Yuejun Luo1,2, Bo Zheng3
1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Background:
Except for B7-CD28 family members, more novel immune checkpoints are being discovered. They are closely associated with tumor immune microenvironment and regulate the function of many immune cells. Various cancer therapeutic studies targeting these novel immune checkpoints are currently in full swing. However, studies concerning novel immune checkpoints phenotypes and clinical significance in lung adenocarcinoma (LUAD) are still limited.
Methods:
We enrolled 1883 LUAD cases from nine different cohorts. The samples from The Cancer Genome Atlas (TCGA) were used as a training set, whereas seven microarray data cohorts and an independent cohort with 102 qPCR data were used for validation. The immune profiles and potential mechanism of the system were also explored.
Results:
After univariate Cox proportional hazards regression and stepwise multivariable Cox analysis, a novel immune checkpoints-based system (LTA, CD160, and CD40LG) were identified from the training set, which significantly stratified patients into high- and low-risk groups with different survivals. Furthermore, this system has been well validated in different clinical subgroups and multiple validation cohorts. It also acted as an independent prognostic factor for patients with LAUD in different cohorts. Further exploration suggested that high-risk patients exhibited distinctive immune cells infiltration and suffered an immunosuppressive state. Additionally, this system is closely linked to various classical immunotherapy biomarkers.
Conclusion:
we constructed a novel immune checkpoints-based system for LUAD, which predicts prognosis and immunotherapeutic implications. We believe that these findings will not only aid in clinical management but will also shed some light on screening appropriate patients for immunotherapy.
Insights
A new immune checkpoint system (LTA, CD160, CD40LG) effectively predicts prognosis and immunotherapy response in lung adenocarcinoma (LUAD). This system identifies high-risk patients with immunosuppressive tumors, aiding clinical management and patient selection for cancer therapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Novel immune checkpoints, beyond the B7-CD28 family, are emerging as key regulators of the tumor immune microenvironment.
- Their role in lung adenocarcinoma (LUAD) and clinical significance remain underexplored.
- Understanding these checkpoints is crucial for advancing cancer therapeutics.
Purpose of the Study:
- To identify and validate a novel immune checkpoint-based system for predicting prognosis in LUAD.
- To explore the association of this system with immune cell infiltration and immunotherapy biomarkers.
- To provide insights for clinical management and patient selection for immunotherapy.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) LUAD cohort as a training set (n=1883).
- Validated findings across seven microarray cohorts and an independent qPCR cohort.
- Employed univariate Cox regression and stepwise multivariable Cox analysis to identify prognostic markers.
Main Results:
- A novel immune checkpoint system comprising LTA, CD160, and CD40LG was identified.
- This system significantly stratified LUAD patients into high- and low-risk groups with distinct survival outcomes.
- High-risk patients demonstrated immunosuppressive tumor microenvironments and correlations with immunotherapy biomarkers.
Conclusions:
- A novel immune checkpoint system (LTA, CD160, CD40LG) serves as an independent prognostic factor for LUAD.
- This system predicts patient prognosis and has implications for immunotherapy response.
- Findings support its utility in clinical decision-making and optimizing immunotherapy selection for LUAD patients.
