A Predictive Model for Tumor Invasion of the Inferior Vena Cava Wall Using Multimodal Imaging in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus.

PURPOSE: Developed a preoperative prediction model based on multimodality imaging to evaluate the probability of inferior vena cava (IVC) vascular wall invasion due to tumor infiltration. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 110 patients with renal cell carcinoma (RCC) with level I-IV tumor thrombus who underwent radical nephrectomy and IVC thrombectomy between January 2014 and April 2019. The patients were categorized into two groups: 86 patients were used to establish the imaging model, and the data validation was conducted in 24 patients. We measured the imaging parameters and used logistic regression to evaluate the uni- and multivariable associations of the clinical and radiographic features of IVC resection and established an image prediction model to assess the probability of IVC vascular wall invasion. RESULTS: In all of the patients, 46.5% (40/86) had IVC vascular wall invasion. The residual IVC blood flow (OR 0.170 [0.047-0.611]; P = 0.007), maximum coronal IVC diameter in mm (OR 1.203 [1.065-1.360]; P = 0.003), and presence of bland thrombus (OR 3.216 [0.870-11.887]; P = 0.080) were independent risk factors of IVC vascular wall invasion. We predicted vascular wall invasion if the probability was >42% as calculated by: {Ln [Pre/(1 - pre)] = 0.185 × maximum cornal IVC diameter + 1.168 × bland thrombus-1.770 × residual IVC blood flow-5.857}. To predict IVC vascular wall invasion, a rate of 76/86 (88.4%) was consistent with the actual treatment, and in the validation patients, 21/26 (80.8%) was consistent with the actual treatment. CONCLUSIONS: Our model of multimodal imaging associated with IVC vascular wall invasion may be used for preoperative evaluation and prediction of the probability of partial or segmental IVC resection.

Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production.

Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells. PD-1 contains an immunoreceptor tyrosine-based inhibitory motif and mice deficient in PD-1 develop autoimmune disorders suggesting a defect in peripheral tolerance. Human PD-L1 and PD-L2 are expressed on immature dendritic cells (iDC) and mature dendritic cells (mDC), IFN-gamma-treated monocytes, and follicular dendritic cells. Using mAbs, we show that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. Enhancement of T cell activation was most pronounced with weak APC, such as iDCs and IL-10-pretreated mDCs, and less pronounced with strong APC such as mDCs. These data are consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of iDC. PD-L1 expression differs from PD-L2 in that PD-L1 is expressed on activated T cells, placental trophoblasts, myocardial endothelium, and cortical thymic epithelial cells. In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells. PD-L1 is also highly expressed on most carcinomas but minimally expressed on adjacent normal tissue suggesting a role in attenuating antitumor immune responses.