PGE inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.

Expansion of antigen-experienced CD8 T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer. Interleukin-2 (IL-2) acts as a key regulator of CD8 cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses.

Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

Background: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors.

Methods: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018.

Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients?

Opinion Statement: Compared to liver and lung metastases, brain metastases (BMs) from colorectal cancer (CRC) are rare and remain poorly investigated despite the anticipated rise in their incidence. CRC patients bearing BM have a dismal prognosis with a median survival of 3-6 months, significantly lower than that of patients with BM from other primary tumors, and of those with metastatic CRC manifesting extracranially. While liver and lung metastases from CRC have more codified treatment strategies, there is no consensus regarding the treatment of BM in CRC, and their management follows the approaches of BM from other solid tumors.

Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu.

The synthesis of a series of novel 3,4-cis- and 3,4-trans-substituted carbocyclic nucleoside analogs from protected uracil and thymine is described. The key reaction in the followed synthetic protocols utilized the Mitsunobu reaction to couple 3,4-substituted cyclopentanols to (3)N-benzoyl uracil or (3)N-benzoyl thymine. These molecules were evaluated with regard to their ability to treat diabetic nephropathy.