Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node.

Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a CD8+ PD-1+ Tcf-1+ stem-like T cell subset in the tumor-draining lymph node (TdLN). Using murine melanoma models, we found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. Our data indicate that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor.

Volumetric Assessment of Pediatric Vascular Malformations Using a Rapid, Hand-Held Three-Dimensional Imaging System.

The effect of percutaneous, surgical, and medical therapies for vascular malformations (VMs) is often difficult to quantify volumetrically using cross-sectional imaging. Volumetric measurement is often estimated with serial, expensive MRI examinations which may require sedation or anesthesia. We aim to explore whether a portable 3D scanning device is capable of rapid, accurate volumetric analysis of pediatric VMs. Using an iPad-mounted infrared scanning device, 3D scans of patient faces, arms, and legs were acquired over an 8-month study period. Proprietary software was use to perform subsequent volumetric analysis. Of a total of 30 unilateral VMs involving either the face, arms, or legs, 26 (86.7%) VMs were correctly localized by discerning the larger volume of the affected side compared to the normal contralateral side. For patients with unilateral facial VMs (n = 10), volume discrepancy between normal and affected sides differed compared with normal controls (n = 19). This was true for both absolute (60 cc ± 55 vs 15 cc ± 8, p = 0.03) as well as relative (18.1% ± 13.2 vs 4.0% ± 2.1, p = 0.008) volume discrepancy. Following treatment, two patients experienced change in leg volume discrepancy ranging from - 17.3 to - 0.4%. Using a portable 3D scanning device, we were able to rapidly and noninvasively detect and quantify volume discrepancy resulting from VMs of the face, arms, and legs. Preliminary data suggests this technology can detect volume reduction of VMs in response to therapy.