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Xiong et al. engineer CAR T cells to express the c-Kit D816V mutation, which enhances antigen-dependent proliferation and cytotoxicity, translates into extended survival in solid tumor models and is controllable by tyrosine kinase inhibitors.
Zhou et. al. report the interim results of the randomized phase III GEMSTONE-302 trial, showing the overall survival benefits of first-line treatment with the PD-L1 inhibitor sugemalimab versus placebo in combination with chemotherapy, in patients with NSCLC.
Sung et. al. identify genetic, molecular and clinical risk factors for immune-related adverse events in multicancer cohorts of patients treated with checkpoint inhibitors and develop predictive models that they validate in an independent cohort.
Adachi et al. describe a mechanism of adaptive resistance to KRAS G12C inhibitors which involves a Scribble mis-localization via palmitoylation and subsequent YAP and MRAS activation that leads to feedback reactivation of MAPK signaling.
Hagenbeek et al. identify a small-molecule pan-TEAD inhibitor that blocks the interaction between YAP/TAZ and TEAD proteins. They demonstrate that treatment with the inhibitor leads to antitumor activity and can synergize with KRAS G12C inhibition.
Malladi and colleagues show that inhibiting DRP1 limits mitochondrial plasticity, resulting in increased mitochondrial fusion, impaired fatty acid oxidation and reduced metastasis formation in breast cancer models.
Bousso and colleagues show that IFN-γ production is the dominant tumor elimination mechanism exerted by CD4+ CAR T cells and define tumor cell sensitivity to IFN-γ as a determinant of CD4+ CAR T efficacy.
Mitsiades and colleagues utilize functional genomics data in over 700 cancer cell lines, to identify genes with preferentially essential functions in multiple myeloma, which may represent targets for precision medicine strategies.
Joyce and colleagues use bulk and single-cell profiling of T cell phenotypes in human samples from primary brain tumors and brain metastases as a resource for understanding the biology and therapeutic relevance of the brain tumor microenvironment.
Merbl and colleagues demonstrate that high expression of the proteasome regulator PSME4 is associated with immune-cold lung tumors and reduced antitumor immune responses, by functioning to modulate the protein degradome and antigen diversity.
Watson et al. demonstrate that astrocyte mitochondria can be horizontally transferred to glioblastoma cells in a GAP43-dependent manner, leading to changes in mitochondrial respiration and metabolism that promote proliferation and tumor growth.
Culbertson et al. profile antisense RNAs using a newly developed computational pipeline and identify NQO1-AS as contributor to breast cancer progression and lung metastasis through regulation of the redox enzyme NQO1.
Ruscetti and colleagues show that the pancreatic cancer tumor microenvironment suppresses immune surveillance following therapy-induced senescence via repression of inflammatory gene expression through EZH2.
Bassani-Sternberg and colleagues perform multiregion immunopeptidomics, genomics and spatial transcriptomics in patient lung cancer samples, demonstrating heterogeneity in the immunopeptidome associated with degrees of immune cell infiltration.
Snijder and colleagues use ex vivo pharmacoscopy and bone marrow composition profiling in a cohort of patients with multiple myeloma to identify tailored therapeutic sensitivities and stratify the cohort into three microenvironmental PhenoGroups.
Akkari and colleagues find that CD103+ regulatory T cells are highly abundant in the glioblastoma environment after checkpoint blockade restraining therapy response, and show therapeutic benefit for combined Treg targeting with radio-immunotherapy.
Getz and colleagues demonstrate a computational approach to estimate the timing of genomic drivers in early tumor progression from cancer types that do not have premalignant disease, using HPV-negative and HPV-positive head and neck squamous cell carcinoma as examples.
Voorwerk et al. report the clinical and translational results from a phase II trial evaluating the combination of carboplatin with anti-PD-L1 in patients with invasive lobular breast cancer, who have been underrepresented in clinical trials so far.