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While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone.
View Article and Find Full Text PDFPD-1 is a key negative regulator of CD8 T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects.
View Article and Find Full Text PDFArticle Synopsis
- - High-grade knee posterolateral corner (PLC) injuries can lead to severe instability and complications like graft failure and early osteoarthritis if improperly diagnosed or treated.
- - PLC reconstruction generally yields better outcomes than repair, with biomechanical studies offering mixed results on techniques; some methods using a separate tibial tunnel for specific ligaments show improved stability.
- - Recent reviews highlight the complexity of PLC injuries, as they often occur with cruciate ligament tears and exhibit various laxity patterns, although both reconstruction techniques demonstrate low rates of complications and failures.
Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity.
Cancer Immunol Res
November 2024
Ragon Institute of Mass General, MIT, and Harvard, Cambridge, Massachusetts.
Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses.
View Article and Find Full Text PDFInfant Suck Strength Exam: Introduction of an Accessible Clinical Technique for Measuring Infant Suck at the Breast.
J Hum Lact
August 2024
Department of Family Medicine, University of North Carolina, School of Medicine, Chapel Hill, NC, USA.
One of the core skills required in lactation support is understanding and correcting ineffective or painful breastfeeding. The behavior being corrected, however, occurs inside the infant's mouth, making it difficult to see and assess. When providing care in the field, we use standardized tools and digital suck exams.
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