Volume 4 Issue 10, October 2023

Charles Swanton obtained a PhD from the Imperial Cancer Research Fund Laboratories (now the Francis Crick Institute) in 1998 and completed his medical oncology and Cancer Research UK (CRUK)-funded postdoctoral clinical scientist training in 2008. He was appointed chair in personalized cancer medicine at the UCL Cancer Institute, and consultant thoracic medical oncologist at UCL Hospitals in 2011. In 2016, he was awarded a Napier Professor in Cancer by the Royal Society, and in 2017 he was appointed principal group leader of the Francis Crick Institute. He is co-director of the Cancer Research UK Lung Cancer Centre of Excellence, and chief clinician of Cancer Research UK.

The development of immunotherapies for acute myeloid leukemia (AML) has been limited by a lack of known tumor-specific targets. A study now shows the feasibility of developing highly sensitive and selective T cell-receptor-based therapies against an HLA-A*02:01-associated peptide derived from a recurrent mutation in a subset of patients with AML.

The nervous system regulates cancer progression, and the importance of neuron–glioma communication in tumor growth is evident in glioblastoma. This tumor-promoting communication presents a potential therapeutic axis, a concept reinforced by a study that identifies a specific potassium channel complex as a therapeutic target.

Immunosuppressive myeloid cells, which are associated with resistance to anti-PD1 therapy in patients with glioblastoma, have high expression of KDM6B, an epigenetic enzyme. Deletion or inhibition of KDM6B reprograms the myeloid cells to an immunostimulatory phenotype and thereby overcomes resistance to anti-PD1 therapy in preclinical models of glioblastoma.

Coukos and colleagues conduct a phase 1 study to evaluate the benefit of adoptive transfer of ex vivo-expanded, vaccine-primed T cells in patients with ovarian cancer—a cancer type that often does not respond to immune checkpoint blockade.

Huang and colleagues identify that EAG2 and Kvβ2 physically interact to form a potassium channel complex in glioblastoma and develop a designer peptide that disrupts their interaction and induces tumor regression.

Zheng et al. show that ChAT-expressing cholinergic T cells suppress the development of liver cancer via their cholinergic activity, which constrains calcium/NFAT signaling induced by TCR engagement.

Goswami and colleagues identify high expression of KDM6B in immune-suppressive myeloid cells in glioblastoma and show that its myeloid cell-specific deletion enhances inflammatory signaling and antigen presentation, thereby extending survival.

Olweus and colleagues identify a T cell receptor reactive against the recurrent D835Y driver mutation in FLT3 in acute myeloid leukemia and show that engineered T cells against this neoantigen provide efficient immunotherapy.

Miller et al. show that blocking ACSS2 remodels acetate metabolism in cancer cells, thereby freeing acetate for tumor-infiltrating lymphocytes, which bolsters their effector function and promotes antitumor immunity in breast cancer.

Wartewig et al. show that PDCD1 in T cell lymphoma restricts glycolytic energy and acetyl-CoA production. Inhibition of PD-1 signaling enforces ACLY activity and generates extramitochondrial acetyl-CoA for histone acetylation to enable AP-1 hyperactivation.