Assessing the Accuracy of an Artificial Intelligence-Based Segmentation Algorithm for the Thoracic Aorta in Computed Tomography Applications.

The aim was to evaluate the accuracy of a prototypical artificial intelligence-based algorithm for automated segmentation and diameter measurement of the thoracic aorta (TA) using CT. One hundred twenty-two patients who underwent dual-source CT were retrospectively included. Ninety-three of these patients had been administered intravenous iodinated contrast. Images were evaluated using the prototypical algorithm, which segments the TA and determines the corresponding diameters at predefined anatomical locations based on the American Heart Association guidelines. The reference standard was established by two radiologists individually in a blinded, randomized fashion. Equivalency was tested and inter-reader agreement was assessed using intra-class correlation (ICC). In total, 99.2% of the parameters measured by the prototype were assessable. In nine patients, the prototype failed to determine one diameter along the vessel. Measurements along the TA did not differ between the algorithm and readers (p > 0.05), establishing equivalence. Inter-reader agreement between the algorithm and readers (ICC ≥ 0.961; 95% CI: 0.940−0.974), and between the readers was excellent (ICC ≥ 0.879; 95% CI: 0.818−0.92). The evaluated prototypical AI-based algorithm accurately measured TA diameters at each region of interest independent of the use of either contrast utilization or pathology. This indicates that the prototypical algorithm has substantial potential as a valuable tool in the rapid clinical evaluation of aortic pathology.

cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes.

Loss of major histocompatibility complex (MHC) class I and interferon-γ (IFN-γ) sensing are major causes of primary and acquired resistance to checkpoint blockade immunotherapy. Thus, additional treatment options are needed for tumors that lose expression of MHC class I. The cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) regulate classical and alternative nuclear factor κB (NF-κB) signaling. Induction of noncanonical NF-κB signaling with cIAP1/2 antagonists mimics costimulatory signaling, augmenting antitumor immunity. We show that induction of noncanonical NF-κB signaling induces T cell-dependent immune responses, even in ß2-microglobulin (ß2M)-deficient tumors, demonstrating that direct CD8 T cell recognition of tumor cell-expressed MHC class I is not required. Instead, T cell-produced lymphotoxin reprograms both mouse and human macrophages to be tumoricidal. In wild-type mice, but not mice incapable of antigen-specific T cell responses, cIAP1/2 antagonism reduces tumor burden by increasing phagocytosis of live tumor cells. Efficacy is augmented by combination with CD47 blockade. Thus, activation of noncanonical NF-κB stimulates a T cell-macrophage axis that curtails growth of tumors that are resistant to checkpoint blockade because of loss of MHC class I or IFN-γ sensing. These findings provide a potential mechanism for controlling checkpoint blockade refractory tumors.