CD4+CD8+ T Cells Represent a Significant Portion of the Anti-HIV T Cell Response to Acute HIV Infection

Previous studies have revealed that HIV infected individuals possess circulating CD4+CD8+ (DP) T-cells specific for HIV antigens. In the present study, we analyzed the proliferation and functional profile of circulating DP T-cells from 30 acutely HIV infected individuals and 10 chronically HIV infected viral controllers. The acutely infected group had DP T-cells which showed more proliferative capability and multifunctionality than both their CD4+ and CD8+ T-cells. DP T-cells were found to exhibit greater proliferation and higher multifunctionality compared to CD4 T-cells in the viral controller group. The DP T-cell response represented 16% of the total anti-HIV proliferative response and greater than 70% of the anti-HIV multifunctional response in the acutely infected subjects. Proliferating DP T-cells of the acutely infected subjects responded to all HIV antigen pools with equal magnitude. Conversely, the multifunctional response was focused on the pool representing Nef, Rev, Tat, VPR and VPU. Meanwhile, the controllers’ DP T-cells focused on Gag and the Nef, Rev, Tat, VPR and VPU pool for both their proliferative and multifunctional responses. Finally, we show that the presence of proliferating DP T-cells following all HIV antigen stimulations is well correlated with proliferating CD4 T-cells while multifunctionality appears to be largely independent of multifunctionality in other T-cell compartments. Therefore, DP T-cells represent a highly reactive cell population during acute HIV infection, which responds independently from the traditional T-cell compartments

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Sensitivity (and 95% CI) of DWI sequences to infarction (in patients with confirmed stroke) stratified by time from symptom onset to imaging.

<p>Sensitivity (and 95% CI) of DWI sequences to infarction (in patients with confirmed stroke) stratified by time from symptom onset to imaging.</p

Cross-tabulation of STEAM-DWI versus HR-DWI and LR-DWI in patients with confirmed stroke.

<p>Cross-tabulation of STEAM-DWI versus HR-DWI and LR-DWI in patients with confirmed stroke.</p

Representative example of agreement between DWI sequences for a patient studied 8 hours after onset of stroke symptoms.

<p>Both low- (A) and high-resolution (B) EPI-DWI show a hyperintensity in the right pons spanning three slices. C) STEAM-DWI also shows a hyperintensity in the right pons. D) FLAIR performed five days after baseline scans confirmed the presence of an infarct in the same location. Ischemic lesions are indicated by red arrows.</p