Refined strategies for the treatment of pancreatic carcinoma: targeting myeloid cells in order to overcome T cell exhaustion

Cancer creates an environment of constant antigen exposure and inflammation. In this setting, T cells transform into a differentiation state that has been termed T cell exhaustion, which is characterised by upregulation of inhibitory receptors, like TIM-3 and PD-1, resulting in loss of effector function. The discovery of receptor-mediated immune checkpoints, which prevent uncontrolled T cell reactions, led to the development of a new class of antibodies termed checkpoint inhibitors, bringing exhaustion phenomena to the forefront of tumour research. Data on the efficacy of checkpoint inhibitors in pancreatic cancer are still sparse; however, preliminary results indicate limited efficacy as single agents. In order to increase therapeutic efficacy, knowledge on T cell exhaustion mechanisms in pancreatic cancer is mandatory. Recently, sophisticated models have confirmed the notion that components of the tumour stroma regulate functionality of intratumoral T cells. Whereas cytotoxic CD8+ effector T cells mark the centrepiece of a successful...
Source: Gut - Category: Gastroenterology Authors: Tags: Commentaries Source Type: research