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Purpose: The AAST Organ Injury Scale is widely adopted for splenic injury severity but suffers from only moderate inter-rater agreement. This work assesses SpleenPro, a prototype interactive explainable artificial intelligence/machine learning (AI/ML) diagnostic aid to support AAST grading, for effects on radiologist dwell time, agreement, clinical utility, and user acceptance., Methods: Two trauma radiology ad hoc expert panelists independently performed timed AAST grading on 76 admission CT studies with blunt splenic injury, first without AI/ML assistance, and after a 2-month washout period and randomization, with AI/ML assistance. To evaluate user acceptance, three versions of the SpleenPro user interface with increasing explainability were presented to four independent expert panelists with four example cases each. A structured interview consisting of Likert scales and free responses was conducted, with specific questions regarding dimensions of diagnostic utility (DU); mental support (MS); effort, workload, and frustration (EWF); trust and reliability (TR); and likelihood of future use (LFU)., Results: SpleenPro significantly decreased interpretation times for both raters. Weighted Cohen's kappa increased from 0.53 to 0.70 with AI/ML assistance. During user acceptance interviews, increasing explainability was associated with improvement in Likert scores for MS, EWF, TR, and LFU. Expert panelists indicated the need for a combined early notification and grading functionality, PACS integration, and report autopopulation to improve DU., Conclusions: SpleenPro was useful for improving objectivity of AAST grading and increasing mental support. Formative user research identified generalizable concepts including the need for a combined detection and grading pipeline and integration with the clinical workflow., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Owing to ease of access and high yield, most murine myeloid-derived suppressor cell (MDSC) knowledge comes from the study of spleen-derived MDSCs rather than those isolated from the tumor. Although several studies have identified subtle differences in suppressive function between these MDSCs, a recent report demonstrated that the whole peripheral myeloid compartment poorly reflects myeloid populations found at the tumor. We confirm and extend these observations by presenting data that indicate extensive differences exist between peripheral and tumor MDSCs, suggesting that it may be inappropriate to use spleen MDSCs as surrogates for studying tumor MDSCs. Using cytospins, we observed that tumor MDSCs have undergone a morphologic shift from immature myeloid cell forms commonly seen in bone marrow (BM) and spleen MDSCs and acquired mature myeloid cell characteristics. Spleen and BM monocyte-like MDSCs (M-MDSCs) readily responded to differentiation signals for multiple myeloid cell types whereas tumor M-MDSCs had remarkably reduced cellular plasticity. At the time of isolation, M-MDSCs from BM or spleen have little to no T cell suppressive activity whereas those from the tumor possess immediate and efficient T cell suppressive function. Finally, microarray analysis revealed that the transcriptomes of tumor and spleen M-MDSCs possessed >4500 differentially expressed transcripts. We conclude that tumor M-MDSCs are more differentiated and mature, and that they are morphologically, genetically, and functionally distinct from spleen and BM M-MDSCs. These observations have important implications for the design of anti-MDSC therapies and suggest that preclinical studies using nontumor MDSCs could lead to results not applicable to tumor MDSCs., (Copyright © 2022 The Authors.)

Myeloid derived suppressor cells (MDSC) suppress the ability of cytotoxic T cells to attack and clear tumor cells from the body. The active form of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH) 2 D), regulates myeloid cell biology and previous research showed that in mouse models 1,25(OH) 2 D reduced the tumor level of CD34+ cells, an MDSC precursor, and reduced metastasis. We tested whether MDSC are vitamin D target cells by examining granulocytic- (G-MDSC) and monocytic (M-MDSC) MDSC from tumors, spleen, and bone marrow. Vitamin D receptor (VDR) mRNA levels are low in MDSC from bone marrow and spleen but are 20-fold higher in tumor MDSC. At all sites, M-MDSC have 4-fold higher VDR mRNA expression than G-MDSC. Bone marrow MDSC were induced to differentiate in vitro into tumor MDSC-like cells by treating with IFN-γ, IL-13, and GM-CSF for 48 h. This treatment significantly elevated Arg1 and Nos2 levels, activated the T cell-suppressive function of MDSC, increased VDR expression 50-fold, and made the MDSC responsive to 1,25(OH) 2 D treatment. Importantly, 1,25(OH) 2 D treatment reduced the T cell suppressive capacity of cytokine-induced total MDSC and M-MDSC by ≥70 % and tumor-derived M-MDSC by 30-50 %. Consistent with this finding, VDR deletion (KO) increased T cell suppressive function of in vitro M-MDSC by 30 % and of tumor-derived M-MDSC by 50 % and G-MDSC by 400 %. VDR KO did not alter Nos2 mRNA levels but significantly increased Arg1 mRNA levels in tumor M-MDSC by 100 %. In contrast, 1,25(OH) 2 D treatment reduced nitric oxide production in both in vitro derived M- and G- MDSC. The major finding of this study is that 1,25(OH) 2 D signaling through the VDR decreases the immunosuppressive capability of MDSC. Collectively, our data suggest that activation of vitamin D signaling could be used to suppress MDSC function and release a constraint on T-cell mediated clearance of tumor cells., (Copyright © 2019. Published by Elsevier Ltd.)