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Cancer immunotherapies have demonstrated durable responses in a range of different cancers. However, only a subset of patients responds to these therapies. We set out to test if non-invasive imaging of tumor perfusion and vascular inflammation may be able to explain differences in T-cell infiltration in pre-clinical tumor models, relevant for treatment outcomes. Tumor perfusion and vascular cell adhesion molecule (VCAM-1) density were quantified using magnetic resonance imaging (MRI) and correlated with infiltration of adoptively transferred and endogenous T-cells. MRI biomarkers were evaluated for their ability to detect tumor rejection 3 days after T-cell transfer. Baseline levels of these markers were used to assess their ability to predict PD-L1 treatment response. We found correlations between MRI-derived VCAM-1 density and infiltration of endogenous or adoptively transferred T-cells in some preclinical tumor models. Blocking T-cell binding to endothelial cell adhesion molecules (VCAM-1/ICAM) prevented T-cell mediated tumor rejection. Tumor rejection could be detected 3 days after adoptive T-cell transfer prior to tumor volume changes by monitoring the extracellular extravascular volume fraction. Imaging tumor perfusion and VCAM-1 density before treatment initiation was able to predict the response of MC38 tumors to PD-L1 blockade. These results indicate that MRI based assessment of tumor perfusion and VCAM-1 density can inform about the permissibility of the tumor vasculature for T-cell infiltration which may explain some of the observed variance in treatment response for cancer immunotherapies.

Through screening of random one-bead one-compound (OBOC) libraries, we previously identified cyclic peptides with the cDGXGXXc motif that bind to α3 integrin subunit on ovarian adenocarcinoma cell lines ES-2, SKOV-3, and CaOV-3. We subsequently synthesized two secondary libraries based on this motif and identified new peptides that bound with a higher affinity to these cell lines. One of the peptides identified from the 20% “down-substituted” focused library was the cdG-HCit-GPQc (“OA02”) peptide. The goal of this study was to determine whether this peptide labeled with near-infrared probes could be detected after intravenous injection in ovarian tumor-bearing mice and if it would selectively localize in the tumor. Three different forms of this peptide were synthesized, “OA02”-biotin (noncovalently linked to streptavidin-Cy5.5); “OA02”-Cy5.5 and “OA02”-AlexaFluo 680. Using a KODAK IS2000MM image station, these peptide probes were used at the near-infrared (NIR) spectra to image nude mice bearing ES-2 (α3 integrin positive) and Raji (α3 integrin negative) xenografts. The peptide probe displayed highly specific tumor uptake within 15 min, which lasted for 70 min for “OA02”-Cy5.5 and “OA02”-AlexaFluo 680 and for 24 hours for “OA02”-biotin-streptavidin-Cy5.5. Some kidney and bladder signal were noted. Prior injection with anti-α3 monoclonal antibody blocked the binding of this peptide to the ES-2 tumors.

This article discusses the importance of the Portal of Amateur Collaborators and the Register of Individual Finds of the Archaeological Map of the Czech Republic (AMCR-PAS) in preserving data from metal-detecting activities in the Czech Republic. The context and legal framework of metal detecting in the country are explained along with the establishment of AMCR-PAS. The collaboration between amateur and professional archaeologists is also discussed. The recorded finds are analysed in terms of chronological, typological and spatial distribution. The AMCR-PAS system is recognised as a crucial tool for the preservation of data from metal detecting, and provides a valuable resource for national and transnational archaeological research, enabled especially by aggregation of AMCR-PAS data in the ARIADNE infrastructure. Overall, this article highlights the significance of the AMCR-PAS system and its potential to contribute to the understanding of the country's rich archaeological heritage. It also examines the shortcomings and challenges that accompany applying the system in practice.

A considerable part of the Czech Republic has been forested with spruce monocultures, which are nowadays at risk of disastrous bark beetle infestation and consequently the destruction of forest stands. Such a development forces us to seek common grounds for landscape conservation and more consistent communication in setting forest management rules. Nevertheless, the trend of rapid deforestation implies a considerable threat to the hitherto unknown but also known archaeological heritage resource. Joint advocacy of the values associated with archaeological sites incorporated within the processes of landscape change assessment constitutes a distinct task aimed at ensuring that such an essential part of the landscape's memory becomes a publicly accepted value.