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Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer
Yuanfeng Wei1, Lingnan Zheng1, Xi Yang1
1Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Background:
Immune checkpoint inhibitors (ICIs) have demonstrated promising outcomes in small cell lung cancer (SCLC), but not all patients benefit from it. Thus, developing precise treatments for SCLC is a particularly urgent need. In our study, we constructed a novel phenotype for SCLC based on immune signatures.
Methods:
We clustered patients with SCLC hierarchically in 3 publicly available datasets according to the immune signatures. ESTIMATE and CIBERSORT algorithm were used to evaluate the components of the tumor microenvironment. Moreover, we identified potential mRNA vaccine antigens for patients with SCLC, and qRT-PCR were performed to detect the gene expression.
Results:
We identified 2 SCLC subtypes and named Immunity High (Immunity_H) and Immunity Low (Immunity_L). Meanwhile, we obtained generally consistent results by analyzing different datasets, suggesting that this classification was reliable. Immunity_H contained the higher number of immune cells and a better prognosis compared to Immunity_L. Gene-set enrichment analysis revealed that several immune-related pathways such as cytokine-cytokine receptor interaction, programmed cell death-Ligand 1 expression and programmed cell death-1 checkpoint pathway in cancer were hyperactivated in the Immunity_H. However, most of the pathways enriched in the Immunity_L were not associated with immunity. Furthermore, we identified 5 potential mRNA vaccine antigens of SCLC (NEK2, NOL4, RALYL, SH3GL2, and ZIC2), and they were expressed higher in Immunity_L, it indicated that Immunity_L maybe more suitable for tumor vaccine development.
Conclusions:
SCLC can be divided into Immunity_H and Immunity_L subtypes. Immunity_H may be more suitable for treatment with ICIs. NEK2, NOL4, RALYL, SH3GL2, and ZIC2 may be act as potential antigens for SCLC.
Insights
This study identified two small cell lung cancer (SCLC) subtypes: Immunity High (Immunity_H) and Immunity Low (Immunity_L). Immunity_H may respond better to immune checkpoint inhibitors, while Immunity_L could be targeted for mRNA vaccine development.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Small cell lung cancer (SCLC) treatment remains challenging, with limited benefit from immune checkpoint inhibitors (ICIs) for many patients.
- Developing precise SCLC therapies necessitates novel patient stratification strategies.
- This research introduces a new SCLC phenotype classification based on immune signatures.
Purpose of the Study:
- To classify SCLC patients into distinct subtypes based on immune profiles.
- To investigate the potential of these subtypes for differential treatment responses, including ICIs and mRNA vaccines.
- To identify novel therapeutic targets within SCLC subtypes.
Main Methods:
- Hierarchical clustering of SCLC patients across three public datasets using immune signatures.
- Tumor microenvironment component analysis utilizing ESTIMATE and CIBERSORT algorithms.
- Identification of potential mRNA vaccine antigens and validation through quantitative reverse transcription PCR (qRT-PCR).
Main Results:
- Two distinct SCLC subtypes were identified: Immunity High (Immunity_H) and Immunity Low (Immunity_L), with consistent classification across datasets.
- The Immunity_H subtype exhibited higher immune cell infiltration and a better prognosis, with enriched immune-related pathways.
- The Immunity_L subtype showed higher expression of five potential mRNA vaccine antigens (NEK2, NOL4, RALYL, SH3GL2, ZIC2), suggesting suitability for vaccine development.
Conclusions:
- SCLC can be reliably classified into Immunity_H and Immunity_L subtypes.
- The Immunity_H subtype is potentially more responsive to immune checkpoint inhibitor therapy.
- NEK2, NOL4, RALYL, SH3GL2, and ZIC2 represent promising candidate antigens for SCLC mRNA vaccine development.
