Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.
View Article and Find Full Text PDFWe report the development of a new oxazole-based cleavable linker to release peptides from attached cargo. Oxazoles are stable to most reaction conditions, yet they can be rapidly cleaved in the presence of single-electron oxidants like cerium ammonium nitrate (CAN). An oxazole linker could be synthesized and attached to peptides through standard solid-phase peptide coupling reactions.
View Article and Find Full Text PDFThe assessment of the cellular heterogeneity and abundance in bulk tissue samples is essential for characterising cellular and organismal states. Computational approaches to estimate cellular abundance from bulk RNA-Seq datasets have variable performances, often requiring benchmarking matrices to select the best performing methods for individual studies. However, such benchmarking investigations are difficult to perform and assess in typical applications because of the absence of gold standard/ground-truth cellular measurements.
View Article and Find Full Text PDFThe immunosuppressive tumor microenvironment constitutes a significant hurdle to immune checkpoint inhibitor responses. Both soluble factors and specialized immune cells, such as regulatory T cells (Treg), are key components of active intratumoral immunosuppression. Inducible costimulatory receptor (ICOS) can be highly expressed in the tumor microenvironment, especially on immunosuppressive Treg, suggesting that it represents a relevant target for preferential depletion of these cells.
View Article and Find Full Text PDFJ Wound Ostomy Continence Nurs
February 2017
Purpose: The purpose of this study was to compare health-related quality of life (HRQOL) in patients receiving preoperative stoma marking by a certified wound, ostomy and continence nurse (CWOCN) to patients who did not receive preoperative marking.
Design: Quasi-experimental, nonrandomized comparison cohort study.
Subjects And Setting: The sample comprised 59 patients immediately following creation of a fecal stoma during an 18-month period between 2008 and 2010.