Quantitative spatial evaluation of tumor-immune interactions in the immunotherapy setting of metastatic melanoma lymph nodes

IntroductionImmune cell infiltration into the tumor microenvironment is generally associated with favorable clinical outcomes in solid tumors. However, the dynamic interplay among distinct immune cell subsets within the tumor-immune microenvironment as it relates to clinical responses to immunotherapy remains unresolved. In this study, we applied multiplex immunofluorescence (MxIF) to spatially characterize tumor-immune interactions within the metastatic melanoma lymph node.MethodsPretreatment, whole lymph node biopsies were evaluated from 25 patients with regionally metastatic melanoma who underwent subsequent anti-PD1 therapy. Cyclic MxIF was applied to quantitatively and spatially assess expression of 45 pathologist-validated antibodies on a single tissue section. Pixel-based single cell segmentation and a supervised classifier approach resolved 10 distinct tumor, stromal and immune cell phenotypes and functional expression of PD1.ResultsSingle cell analysis across 416 pathologist-annotated tumor core regions of interest yielded 5.5 million cells for spatial evaluation. Cellular composition of tumor and immune cell subsets did not differ in the tumor core with regards to recurrence outcomes (p>0.05) however spatial patterns significantly differed in regional and paracrine neighborhood evaluations. Specifically, a regional community cluster comprised of primarily tumor and dendritic cells was enriched in patients that did not experience recurrence (p=0.009). By an independent spatial approach, cell-centric neighborhood analyses identified an enrichment for dendritic cells in cytotoxic T cell (CTL) and tumor cell-centric neighborhoods in the no recurrence patient response group (p<0.0001). Further evaluation of these neighborhoods identified an enrichment for CTL-dendritic cell interactions in patients that did not experience recurrence (p<0.0001) whereas CTL-macrophage interactions were more prevalent in CTL-centric neighborhoods of patients who experienced recurrence (p<0.0001).DiscussionOverall, this study offers a more comprehensive evaluation of immune infiltrates and spatial-immune signatures in the metastatic tumor-immune microenvironment as it informs recurrence risk following immunotherapy

Single beat 3D echocardiography for the assessment of right ventricular dimension and function after endurance exercise: Intraindividual comparison with magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Our study compares new single beat 3D echocardiography (sb3DE) to cardiovascular magnetic resonance imaging (CMR) for the measurement of right ventricular (RV) dimension and function immediately after a 30 km run. This is to validate sb3DE against the "gold standard" CMR and to bring new insights into acute changes of RV dimension and function after endurance exercise.</p> <p>Methods</p> <p>21 non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000, matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5 Tesla) and blood tests before and immediately after each athlete ran 30 km. The runners were not allowed to rehydrate after the race. The order of sb3DE and CMR examination was randomized.</p> <p>Results</p> <p>Sb3DE for the acquisition of RV dimension and function was feasible in all subjects. The decrease in mean body weight and the significant increase in hematocrit indicated dehydration. RV dimensions measured by CMR were consistently larger than measured by sb3DE.</p> <p>Neither sb3DE nor CMR showed a significant difference in the RV ejection fraction before and after exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by sb3DE, this decrease of RV volumes was not significant.</p> <p>Conclusion</p> <p>First, both methods agree well in the acquisition of systolic RV function. The dimensions of the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV volumes decrease significantly when measured by CMR compared to baseline.</p> <p>Second, endurance exercise seems not to induce acute RV dysfunction in athletes without rehydration.</p