Immunotherapy articles from across Nature Portfolio

Optimization of energy and carbon–nitrogen allocation maximizes the proliferation and functionality of chimeric antigen receptor (CAR)-T cells. Lakhani et al. report that tonic signalling elements (scFvs) affect CAR-T cell metabolic fitness in an antigen-independent manner. A modest carbon–nitrogen emission (overflow) and resilient metabolic phenotype (compatibility) are associated with effective CAR-T cell therapy.

T cell infiltration in the tumour microenvironment (TME) is a prerequisite for sustained antitumour immune responses. However, identifying predictive biomarkers that quantify T cell infiltration and the presence of proinflammatory TMEs associated with immune-checkpoint inhibitor (ICI) response for clinical implementation has proved challenging. Here, we highlight a study that validates a T cell-to-stroma enrichment score generated from RNA sequencing data as a novel biomarker for ICI response in patients with urothelial carcinoma.

The mechanical sensor PIEZO1 regulates the traction force that is critical for cytotoxic T cells to target tumour cells. This finding creates avenues for enhancing the efficacy of T cell-targeted immune therapies.

Tumour-derived prostaglandin E₂, signaling through its receptors EP₂ and EP₄, is shown to restrain the responses of tumour-infiltrating stem-like TCF1⁺CD8⁺ T lymphocytes, and modulation of T cell EP₂ and EP₄ can restore anticancer immunity.

Lakhani et al. offer insight into the metabolic reconfigurations driven in T cells by chimeric antigen receptors (CARs) that differ only in their extracellular domains.

Prostaglandin E2 from the tumour microenvironment impairs interleukin-2 sensing by tumour-infiltrating lymphocytes, restricting proliferative response and promoting T cell death via metabolic impairment and ferroptosis. 

The hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate antitumour innate immune responses via endoplasmic reticulum stress in antigen-presenting cells.

Optimization of energy and carbon–nitrogen allocation maximizes the proliferation and functionality of chimeric antigen receptor (CAR)-T cells. Lakhani et al. report that tonic signalling elements (scFvs) affect CAR-T cell metabolic fitness in an antigen-independent manner. A modest carbon–nitrogen emission (overflow) and resilient metabolic phenotype (compatibility) are associated with effective CAR-T cell therapy.

T cell infiltration in the tumour microenvironment (TME) is a prerequisite for sustained antitumour immune responses. However, identifying predictive biomarkers that quantify T cell infiltration and the presence of proinflammatory TMEs associated with immune-checkpoint inhibitor (ICI) response for clinical implementation has proved challenging. Here, we highlight a study that validates a T cell-to-stroma enrichment score generated from RNA sequencing data as a novel biomarker for ICI response in patients with urothelial carcinoma.

The mechanical sensor PIEZO1 regulates the traction force that is critical for cytotoxic T cells to target tumour cells. This finding creates avenues for enhancing the efficacy of T cell-targeted immune therapies.

Identifying which patients will benefit most from immune checkpoint blockade (ICB) is an important clinical challenge. A study now finds that Vδ1⁺ γδ T cells are associated with better response to ICB in melanoma tumors with a lower neoantigen load and shows that some effector functions of PD-1⁺ Vδ1⁺ T cells are repressed after engagement of PD-1 by PD-L1.