CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy.

Cancer patients often receive a combination of antibodies targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA4). We conducted a window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC) to examine the contribution of anti-CTLA4 to anti-PD-L1 therapy. Single-cell profiling of on- versus pre-treatment biopsies identified T cell expansion as an early response marker. In tumors, anti-PD-L1 triggered the expansion of mostly CD8+ T cells, whereas combination therapy expanded both CD4+ and CD8+ T cells. Such CD4+ T cells exhibited an activated T helper 1 (Th1) phenotype. CD4+ and CD8+ T cells co-localized with and were surrounded by dendritic cells expressing T cell homing factors or antibody-producing plasma cells. T cell receptor tracing suggests that anti-CTLA4, but not anti-PD-L1, triggers the trafficking of CD4+ naive/central-memory T cells from tumor-draining lymph nodes (tdLNs), via blood, to the tumor wherein T cells acquire a Th1 phenotype. Thus, CD4+ T cell activation and recruitment from tdLNs are hallmarks of early response to anti-PD-L1 plus anti-CTLA4 in HNSCC.

Outpatient urine collection methods for paediatric urinary tract infections: Systematic review of diagnostic accuracy studies.

AIM: To investigate the diagnostic test accuracy of urine collection methods for urinary tract infections in outpatient children. METHODS: A systematic literature review until April 2021 (Medline, Web of Science, Embase, Cinahl) to examine the diagnostic test accuracy of urine culture on collection methods for urinary tract infection in outpatient children below 18 years. Contamination rates were studied as secondary outcome. The risk of bias was assessed using the QUADAS-2 criteria. Two-by-two tables were extracted in duplicate to calculate sensitivities, specificities, and likelihood ratios with 95% confidence intervals. RESULTS: The search identified seven relevant studies. Clean catch compared to catheterization in children less than 90 days showed a sensitivity and specificity of 97% and 89% (95% CI: 84%-100% and 67%-99%), respectively. Adhesive bags compared to catheterization showed a sensitivity of 83% (95% CI: 75%-90%) and specificity of 91% (95% CI: 83%-96%). There was a similar diagnostic accuracy when comparing urine sampling by means of adhesive bags versus nappy pads. The contamination rate was 5% for clean catch, 30%-80% for adhesive bags and 64% for nappy pads. CONCLUSION: Nappy pads and adhesive bags are easy to use with comparable accuracy but are extremely prone to contamination. Clean-catch urine sampling might be an accurate alternative in young infants in ambulatory care.