Volume 3 Issue 4, April 2022

Cancer vaccines can elicit tumor-specific T cells, but sustaining their function via immune checkpoint therapy (ICT) may be required for robust anti-tumor immunity. A new study reveals that neoantigen cancer vaccines synergize with anti-PD-L1 ICT in a preclinical model and provides mechanistic insights into this synergy.

Patients with KRAS-mutant colorectal cancers do not respond to cetuximab, a monoclonal antibody against EGFR. A new proof-of-concept study presents a bispecific antibody with the ability to trigger EGFR degradation in LGR5⁺ cancer stem cells, and robust anti-tumor activity in KRAS-mutant and wild-type colorectal cancers.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have revolutionized the treatment of EGFR-mutant non-small cell lung cancer; however, secondary resistance limits their efficacy, emphasizing the need for newer approaches. A study now shows preclinical development of allosteric EGFR inhibitors that overcome acquired therapy resistance.

Mitochondrial fission in macrophages is essential for the phagocytosis of tumor cells. Resistance of tumor cells to phagocytosis involves overexpression of GFPT2, an enzyme involved in glutamine metabolism; this results in lower nutrient availability for macrophages to support mitochondrial fission and prevents assembly of the phagocytic machinery.

Llovet and colleagues review recent advances in hepatocellular carcinoma therapy and the clinical workflows for the selection and monitoring of patients undergoing systemic therapies and immunotherapy.

Jänne and colleagues discover and characterize an allosteric EGFR inhibitor with efficacy against therapy-resistant mutations and show preclinical efficacy as monotherapy and in combination in patient-derived xenograft models.

Batlle and colleagues develop an organoid platform for functional antibody screening and identify a therapeutic bispecific antibody that binds EGFR and LGR5 and that shows efficacy across epithelial tumor patient-derived xenograft models in vivo.

Li and colleagues use single-cell techniques to identify features of T cells in the tumor and draining lymph nodes involved in the efficacy of immune checkpoint blockade combined with a neoantigen vaccine in preclinical models.

Li et al. demonstrate mitochondrial fission in macrophages as key for phagocytosis induced by therapeutic antibodies. They identify overexpression of GFPT2 as an inhibitor of the process and phase transition of the phagocytic machinery as its regulator.

Alborzinia et al. report that MYCN-amplified neuroblastoma undergoes ferroptosis in the absence of intracellular cysteine, suggesting a combination of cysteine depletion and concomitant GPX4 inactivation as a potential therapeutic approach.

Hongu et al. find that perivascular macrophages stimulate activation of the pro-metastatic vascular niche via tenascin C stimulation of TLR4 and show that combined TLR4 and VEGF inhibition prevents TNC-mediated metastatic vascular activity.

Danko and colleagues develop BayesPrism, a bulk RNA sequencing deconvolution tool to infer cell type composition and cell-specific expression levels across clinical cancer datasets.