Research Highlights in 2021

Pfister et al. demonstrate a role for unconventionally activated CD8⁺PD1⁺ T cells in NASH-HCC, which limits response to immunotherapy.

Bertocchi et al. show that tumour-resident bacteria in colorectal cancer disseminate to the liver via an impaired gut vascular barrier and promote the liver pre-metastatic niche.

Tello-Lafoz et al. find that the increased rigidity of cancer cells during metastasis can result in a biophysical vulnerability to killing by cytotoxic lymphocytes through a form of mechanosurveillance.

Two recent papers describe the development of bispecific antibodies that specifically target neoantigens derived from common oncogenic mutations.

Gao, Xia, Li, Zhang et al. show that a circular RNA-encoded variant of E-Cadherin stimulates EGFR signalling independently of EGF, and contributes to glioblastoma tumorigenesis and anti-EGFR therapy resistance.

Butler and Cafaro et al. identify a mechanism of MYC inhibition by uropathogenic Escherichia coli that may have therapeutic potential in cancer.

Biswas et al. show that B cell infiltration in ovarian cancer leads to humoral immune responses dominated by polyclonal IgA, which mark ovarian cancer cells to be removed by myeloid cells, and also sensitize cancer cells to T cell-mediated cytolysis thereby controlling tumour growth.

Two recent papers report the first-in-human clinical trials investigating the efficacy and safety of faecal microbiota transplantation for metastatic melanoma that is refractory to cancer immunotherapy.

Yuan, Flores et al. find that NSD3, which encodes a histone H3 lysine 36 methyltransferase, is likely an important of driver of a subset of lung squamous cell carcinomas and show that these tumours may be sensitive to bromodomain inhibitors.

Yu and Green et al. describe a novel mechanism of systemic immunosuppression by liver metastases, whereby intrahepatic myeloid cells induce apoptosis of activated, tumour-specific T cells.

Chen et al. find that arsenic trioxide (ATO), an FDA-approved agent for acute promyelocytic leukaemia, can rescue common p53 structural mutants and restore p53 function.

Bartok, Pataskar, Nagel et al. show that long-term interferon γ-induced tryptophan degradation interferes with mRNA translation in melanoma. They reveal a mechanism by which indoleamine 2,3-dioxygenase 1 and amino acid starvation-dependent ribosomal frameshifting leads to immunogenic aberrant peptide presentation.