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Bodenmiller and colleagues present a method for three-dimensional analysis of tissue architecture using imaging mass cytometry and demonstrate the utility in resolving cellular interactions in the tumor microenvironment, in human breast cancer samples.
Ghajar and colleagues report that astrocyte-deposited laminin-211 promotes the quiescence of disseminated tumor cells in the brain, in a manner dependent on the cytoplasmic sequestration of YAP by dystroglycan.
Zhang and colleagues analyzed patients with lung cancer treated with anti-PD-1 with single-cell methods, finding the presence of precursor exhausted T cells in responders that accumulated through local expansion and clonal revival from peripheral T cells.
Bravo-Cordero and colleagues demonstrate that disseminated tumor cells remodel the extracellular matrix by secreting collagen III and generate a stromal architecture that favors dormancy through DDR1 and STAT1 signaling.
Zhang and colleagues perform systematic multiomics and functional integration of cell-surface proteins and develop a comprehensive catalog of cell-surface actionable targets across cancer, with a practical web platform to explore these data.
Zhang and colleagues report a function of the glycolytic enzyme α-Enolase 1 in iron homeostasis. In this setting it promotes the mRNA decay of IRP1, thereby suppressing ferroptosis in hepatocellular carcinoma.
Kang and colleagues demonstrate that pharmacological targeting of the MTDH1–SND1 axis prevents immune evasion during metastatic progression and provides a synergistic combination strategy with immune-checkpoint blockade to treat metastasis.
Kang and colleagues identify a specific compound blocking MTDH1–SND1 interaction, which prevents metastatic breast cancer progression, induces regression of established metastasis in preclinical models and restores chemosensitivity.
In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy.
Peinado and colleagues show that small extracellular vesicles and secreted NGFR cargo induce lymphangiogenesis and develop the lymph node pre-metastatic niche to promote melanoma metastasis, which could be targeted pre-clinically with NGFR inhibition.
Blanpain and colleagues identify NR2F2 as a regulator of stemness and invasiveness that promotes tumor renewal and restricts differentiation to sustain squamous cell carcinomas.
Lehtiö and colleagues perform proteogenomic analysis of non-small cell lung cancer and identify molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets and validate their classification method in separate clinical cohorts.
Woermann and colleagues describe a deaminase-independent function for APOBEC3A in initiating chromosomal instability and STING-dependent metastasis in human and mouse pancreatic cancer.
Ting and colleagues report the safety and efficacy of combined radiation and immunotherapy in a phase II trial on patients with MSS colorectal or pancreatic cancer and observe that disease control correlates with higher repetitive RNA transcription.
Singh and colleagues show that PDAC phenotypic plasticity is regulated via AP1 enhancer remodeling and modulated by TNF-α+ macrophages and pharmacological inhibition of the BRD4–cJUN–CCL2–TNF-α axis restores favorable PDAC subtypes and prognosis.
Durocher and colleagues identify CIP2A through synthetic lethal CRISPR screens as a key regulator of adaptive feedback mechanisms controlling chromosomal stability arising from accumulated DNA lesions in BRCA-mutated tumor cells.
Sarry and colleagues demonstrate that adaptive resistance to venetoclax + cytarabine therapy in acute myeloid leukemia relies on mitochondrial respiration and show that combination with electron transport chain complex inhibitors delays relapse in patient-derived xenograft models in vivo.
Wu et al. show that LILRB3 modulates AML cell survival and antileukemic T-cell responses through regulation of TRAF2–cFLIP–NF-κB signaling and demonstrate the therapeutic efficacy of LILRB3-blocking antibodies in humanized PDX models in vivo.
Zhai et al. identify clinical brain-penetrant BACE1 inhibitors as regulators of macrophage-dependent phagocytosis in glioblastoma through IL-6–STAT3 signaling and demonstrate preclinical therapeutic efficacy in orthotopic mouse models and PDXs.
Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.