Decoding the Molecular Basis of the Specificity of an Anti-sTn Antibody.

The mucin -glycan sialyl Tn antigen (sTn, Neu5Acα2-6GalNAcα1--Ser/Thr) is an antigen associated with different types of cancers, often linked with a higher risk of metastasis and poor prognosis. Despite efforts to develop anti-sTn antibodies with high specificity for diagnostics and immunotherapy, challenges in eliciting high-affinity antibodies for glycan structures have limited their effectiveness, leading to low titers and short protection durations. Experimental structural insights into anti-sTn antibody specificity are lacking, hindering their optimization for cancer cell recognition.

Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer.

Unlabelled: The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of fibroblasts as part of the host response to cancer. Using single-cell RNA sequencing, multiplex immunostaining, and several genetic mouse models, we identify carcinoma-associated fibroblasts (CAF) with opposing functions in PDAC progression. Depletion of fibroblast activation protein (FAP)+ CAFs results in increased survival, in contrast to depletion of alpha smooth muscle actin (αSMA)+ CAFs, which leads to decreased survival.