Identification of tumor antigens and immune subtypes of acute myeloid leukemia for mRNA vaccine development

Abstract

Background Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy, and there has not been any significant improvement in therapy of AML over the past several decades. The mRNA vaccines have become a promising strategy against multiple cancers, however, its application on AML remains undefined. In this study, we aimed to identify novel antigens for developing mRNA vaccines against AML and explore the immune landscape of AML to select appropriate patients for vaccination. Methods Genomic data and gene mutation data were retrieved from TCGA, GEO and cBioPortal, respectively. GEPIA2 was used to analyze differentially expressed genes. The single cell RNA-seq database Tumor Immune Single-cell Hub (TISCH) was used to explore the association between the potential tumor antigens and the infiltrating immune cells in the bone marrow. Consensus clustering analysis was applied to identify distinct immune subtypes. The correlation between the abundance of antigen presenting cells and the expression level of antigens was evaluated using Spearman correlation analysis. The characteristics of the tumor immune microenvironment in each subtype were investigated based on single-sample gene set enrichment analysis. Results Five potential tumor antigens were identified for mRNA vaccine from the pool of overexpressed and mutated genes, including CDH23, LRP1, MEFV, MYOF and SLC9A9, which were associated with infiltration of antigen-presenting immune cells (APCs). AML patients were stratified into two immune subtypes Cluster1 (C1) and Cluster2 (C2), which were characterized by distinct molecular and clinical features. C1 subtype demonstrated an immune-hot and immunosuppressive phenotype, while the C1 subtype had an immune-cold phenotype. Furthermore, the two immune subtype showed remarkably different expression of immune checkpoints, immunogenic cell death modulators and human leukocyte antigens. Conclusion CDH23, LRP1, MEFV, MYOF and SLC9A9 were potential antigens for developing AML mRNA vaccine, and AML patients in immune subtype 1 were suitable for vaccination. Supplementary Information The online version contains supplementary material available at 10.1007/s12094-023-03108-6.

Classification of Brainstem Gliomas Based on Tumor Microenvironment Status

“…Mounting evidence has supported the fundamental role of TME in tumor genesis and progression [15,16], thus significantly impacting the tumor recurrence, prognosis, and therapeutic response [17]. Additionally, TME classification models have been reported for a variety of tumor types, which have been reported as valuable for predicting prognosis and selecting treatment [15,19,20]. Therefore, a comprehensive understanding of TME is essential for the precise diagnosis and thus better management of BSGs.…”

“…These findings are consistent with previous reports that DIPG is innately resistant to an immune checkpoint blockade [12] and also suggest their unique TME features from gliomas in the other part of the brain. Meanwhile, recent advances in the TME investigation have promoted the development of a series of TME classification models for a variety of malignancies [15,[18][19][20]. Based on inter-tumoral variations in TME components, these models provided clinicians with a useful tool for predicting therapeutic repones and patients' survival, as well as facilitating the development of novel therapeutics [15,[18][19][20].…”

“…Meanwhile, recent advances in the TME investigation have promoted the development of a series of TME classification models for a variety of malignancies [15,[18][19][20]. Based on inter-tumoral variations in TME components, these models provided clinicians with a useful tool for predicting therapeutic repones and patients' survival, as well as facilitating the development of novel therapeutics [15,[18][19][20]. In gliomas, a three-subtype TME model suggests that its IS3 subtype would have a better response to mRNA-based anti-tumor vaccination [19].…”

mRNA vaccine development and applications: A special focus on tumors (Review)

“…A small number of mRNA cancer vaccine clinical studies have been conducted so far ( 122 ). The majority of trials have focused on acute myeloid leukemia (AML) ( 123 ), multiple myeloma ( 124 ), mesothelioma ( 125 ), glioblastoma ( 126 ), malignant glioma ( 127 ) and renal cell carcinoma ( 128 ), as well as mRNA vaccines for pancreatic cancer ( 129 ), melanoma ( 130 ), BCa ( 131 ), non-small cell lung cancer ( 132 ), prostate cancer ( 133 ), ovarian cancer ( 134 ) and colorectal cancer ( 135 ) and are still in their early stages (I and II) ( 136 - 140 ) ( Fig. 5 ).…”

What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?

“…Yet, there is little information about their somatic mutations in cancer. Somatic mutations in SLC16A1 [ 18 ], SLC16A7 [ 24 , 64 ], SLC9A2 [ 91 ], SLC9A3 [ 42 ], SLC9A8 [ 48 ], SLC9A9 [ 31 , 85 ], SLC4A2 [ 22 , 88 ], SLC4A4 [ 53 ], SLC4A7 [ 34 ], and SLC4A8 [ 47 ] have been reported in human cancers (Table 1 ). However, their abundance across large pan-cancer cohorts has not been analysed.…”