Cytotoxic T cells articles from across Nature Portfolio

Interactions between Semaphorin-3A (SEMA3A) and Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 have been shown to affect T cell development. Here the authors investigate how these interactions affect CD8⁺ T cells in tumour immunity, showing that NRP-1, Plexin-A1 and Plexin-A4 are upregulated on T cells allowing tumour derived SEMA3A to inhibit CD8⁺ T cell migration and function.

The heterogeneity in naive CD8⁺ T cells is essential for diverse immune responses. Here the authors show that variations in developmental self-reactivity of CD8⁺ T cells influence their differentiation into T_c17 cells in inflammatory conditions.

Obesity represents a risk factor for cancer and compromises immune function, however the mechanisms linking the two together are not fully known. Here authors show in a mouse sarcoma model that obesity increases tumour incidence, impairs intra-tumoral T cell immunity but paradoxically increases sensitivity to immune therapy via impairing immunoediting.

The migration of T cells into tumours and how this is regulated by metabolic pathways is not completely understood. Here the authors use human and xenograft mouse models to explore the functional changes in T cells during migration in tumours and how glycolytic and TCA cycle metabolism is involved.

The reasons for why hepatocellular carcinoma (HCC) is unresponsive to anti-PD-1 inhibition in some patients is not fully understood. Here the authors use human samples and mice tumour models to implicate serum amyloid A and STAT3 signalling involvement in the resistance to anti-PD1 immunotherapy in HCC.

Cell softness protects cytotoxic T lymphocytes (CTL) from autolysis by own soluble factors such as perforin secreted for killing target cells. Here the authors show that softness can be induced by YAP activation, and that T leukemic cells are more sensitive to YAP inhibition than CTLs, thereby hinting YAP inhibitors as a potential therapy for T leukemia.

The failure of T cell-targeted vaccines for HIV in clinical trials is likely due to impaired degranulation of low-avidity CD8⁺ T cells in the context of low levels of antigen presentation.

Glucose transporter-mediated uptake of glucose is a key metabolic checkpoint in T cells. Fu et al. have identified GLUT2 as a critical regulator of CD8⁺ T cell metabolism and function in response to glucose and oxygen availability.

Gillian Griffiths and colleagues show that T cell receptor downregulation at the immune synapse occurs through ectocytosis, which terminates receptor signalling and promotes dissociation from target cells.

A preprint by Lerner et al. shows that conventional CD8⁺ T cells can kill tumour cells lacking MHC class I expression in an NKG2D-dependent manner.

Lactate build up in the tumour microenvironments is thought to dampen anti-tumour immunity, but in vitro pre-conditioning T cells with lactate enhances anti-tumour activity in vivo in pre-clinical mouse models.