A CIBERSORTx-based immune cell scoring system could independently predict the prognosis of patients with myelodysplastic syndromes

Abstract

Aside from the cell-intrinsic factors such as genetic alterations, immune dysregulation in the bone marrow (BM) microenvironment plays a role in the development and progression of myelodysplastic syndromes (MDS). However, the prognostic implications of various immune cells in MDS patients remain unclear. We adopted CIBERSORTx to estimate the relative fractions of 22 subtypes of immune cells in the BM of 316 MDS patients and correlated the results with clinical outcomes. A lower fraction of unpolarized M0 macrophages and higher fractions of M2 macrophages and eosinophils were significantly associated with inferior survival. An immune cell scoring system (ICSS) was constructed based on the proportion of these three immune cells in the BM. The ICSS high-risk patients had higher BM blast counts, higher frequencies of poor-risk cytogenetics, and NPM1, TP53, and WT1 mutations than intermediate- and low-risk patients. The ICSS could stratify MDS patients into three risk groups with distinct leukemia-free survival and overall survival among the total cohort and in the subgroups of patients with lower and higher disease risk based on the revised International Prognostic Scoring System (IPSS-R). The prognostic significance of ICSS was also validated in another independent cohort. Multivariable analysis revealed that ICSS independently predicted prognosis, irrespective of age, IPSS-R, and mutation status. Bioinformatic analysis demonstrated a significant correlation between high-risk ICSS and nuclear factor kappa B signaling, oxidative stress, and leukemic stem cell signature pathways. Further studies investigating the mechanistic insight into the crosstalk between stem cells and immune cells are warranted.

An inflammation-related gene landscape predicts prognosis and response to immunotherapy in virus-associated hepatocellular carcinoma

“…The immune infiltration characteristics (the immune and stromal scores) of virus-related HCC, based on the RNA-seq dataset of TCGA database LIHC, were evaluated by ESTIMATE algorithm ( 30 ). Then, CIBERSORTx was applied to quantify the percentages of 22 immune cell subtypes of each patient in the TME ( 31 ). Also, the correlation between the subsets on PD-1, PD-L1, and CTLA-4 expression was assessed.…”

Human fetal cerebellar cell atlas informs medulloblastoma origin and oncogenesis

“…Patient cohorts were sub-grouped based on the TCP score (the estimated proportion of TCP). The TCP score was calculated based on the previously described scoring system with CIBERSORTx deconvolution analyses 19,54 of the proportion of TCP cells against bulk transcriptomes of human MB subgroups (differentially expressed genes) from Cavalli’s MB cohort dataset. P values of survival curves were reported using the log-rank test.…”

Whole transcriptome sequencing reveals HOXD11-AGAP3, a novel fusion transcript in the Indian acute leukemia cohort

“…Newman et al developed a method to fractionate the immune cells using gene expression, CIBERSORT (Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts) ( Newman et al, 2015 ). It has been utilized in AML patients to predict inferior event-free survival (EFS) and overall survival (OS) and identifying novel prognostic markers ( Wang et al, 2021 ). The relative presence of M0 vs. M2 macrophages predicted the relapse.…”

“…The relative presence of M0 vs. M2 macrophages predicted the relapse. Apart from the available risk stratification markers, the immune cell scoring system (ICSS) can be used as an independent prognostic predictor ( Wang et al, 2021 ).…”