Lipotoxicity as a Barrier for T Cell-Based Therapies

Abstract

Nowadays, T-cell-based approaches play an increasing role in cancer treatment. In particular, the use of (genetically engineered) T-cells has heralded a novel era for various diseases with previously poor outcomes. Concurrently, the relationship between the functional behavior of immune cells and their metabolic state, known as immunometabolism, has been found to be an important determinant for the success of immunotherapy. In this context, immune cell metabolism is not only controlled by the expression of transcription factors, enzymes and transport proteins but also by nutrient availability and the presence of intermediate metabolites. The lack of as well as an oversupply of nutrients can be detrimental and lead to cellular dysfunction and damage, potentially resulting in reduced metabolic fitness and/or cell death. This review focusses on the detrimental effects of excessive exposure of T cells to fatty acids, known as lipotoxicity, in the context of an altered lipid tumor microenvironment. Furthermore, implications of T cell-related lipotoxicity for immunotherapy will be discussed, as well as potential therapeutic approaches.

A Patent Review on SARS Coronavirus Papain‐Like Protease (PLpro) Inhibitors

“…A week later on 26 August 2021, researchers at the University of Konstanz filed a patent disclosing curcumin (Figure 31; WO 2022/043435; Table 1), a diarylheptanoid found in Curcuma longa (ginger), exhibited SARS-CoV-2 PL pro inhibitory activity (IC 50 26 μM). [53] Curcumin has also been reported to…”

Implementation of Immunometabolism into Curricula, Scientific Societies, and Immunological Routine Diagnostics

“…This enables CAR T cells to bind and kill tumour cells when reinfused to patients. What looks in theory like a universal form of treatment for malignant diseases is in reality confronted with varying success also due to challenges in maintaining metabolic fitness of CAR T cells during manufacturing or after CAR T cells have been administered to the patient 15,16,17 . Here, further studies are needed especially with the increasing number of diseases that can be efficiently targeted by CAR T cells.…”