Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma.

Background: Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear.

The correlation between LAG-3 expression and the efficacy of chemoimmunotherapy in advanced biliary tract cancer.

In our previous phase II T1219 trial for advanced biliary tract cancer (ABTC), the combination of nivolumab with modified gemcitabine and S-1 exhibited promising efficacy, while the programmed-death-ligand-1 (PD-L1) expression did not predict chemoimmunotherapy efficacy. Lymphocyte-activation-gene-3 (LAG-3), a negative immune checkpoint, is frequently co-expressed with PD-L1. This study assessed the predictive value of LAG-3 expression in ABTC patients who received chemoimmunotherapy.

Energetics of substrate transport in proton-dependent oligopeptide transporters.

The PepT transporter mediates the transport of peptides across biological membranes. Despite advancements in structural biology, including cryogenic electron microscopy structures resolving PepT in different states, the molecular basis of peptide recognition and transport by PepT is not fully elucidated. In this study, we used molecular dynamics simulations, Markov State Models (MSMs), and Transition Path Theory (TPT) to investigate the transport mechanism of an alanine-alanine peptide (Ala-Ala) through the PepT transporter.

Hidradenitis Suppurativa: A Review of the Biologic and Small Molecule Immunomodulatory Treatments.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that presents as painful, deep-seated nodules, sinus tracts, and abscesses in about 1% of the population. Although the pathogenesis of HS is not perfectly understood, it is generally recognized to be caused by a combination of genetic, endocrine, environmental, and microbiological factors. The treatment principles of HS focus on decreasing the microbial load with antibiotics and/or modulating the host immune response to reduce inflammation.