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Rezvan and colleagues profile the infusion product from individuals with DLBCL treated with CAR T cells and integrate functional profiling by timelapse imaging microscopy and scRNA-seq to identify a signature of migratory CD8+ T cells associated with response.
Zeiser and colleagues show that CAR T cell therapy results in upregulation of the TGFβ-activated kinase-1 (TAK1)–NF-κB–p38 MAPK pathway in microglia, causing neurocognitive defects, and find that TAK1 inhibition can reduce immune effector cell-associated neurotoxicity syndrome.
In this phase 1 trial, Hegde et al. treat 13 individuals with advanced sarcoma with lymphodepletion followed by HER2-specific CAR T cells, which were found to be safe and showed antitumor activity.
Merz and colleagues perform single-cell multiomic analysis of mononuclear cells isolated from individuals receiving BCMA-directed CAR T cell therapy for myeloma and show that nonresponders are characterized by an immune-suppressive microenvironment.
Lawson et al. show that genetic inactivation of Phd1 or Phd2 hinders progression of AML and compromises leukemic stem cells. They develop a selective PHD inhibitor IOX5 and show therapeutic efficacy in AML, which can be potentiated with venetoclax.
Ye and colleagues show that an oncolytic virus that delivers tumor-irrelevant bystander T cell epitopes to tumor cells can exploit the abundant population of bystander T cells in the tumor for anti-tumor immunity and potentiate cancer immunotherapy.
Chapeau et al. develop a nonallosteric inhibitor of the interaction between YAP and all four TEAD proteins. Treatment with the inhibitor, either as monotherapy or in combination with other treatment modalities, leads to induction of cell death in several in vivo cancer models.
Guida et al. assess seven measures of biological age in SJLIFE Cohort and reveal that survivors of cancer age faster than healthy controls and have increased risk of frailty and death. The aging trajectory is further affected by cancer type and therapy.
Rich and colleagues show that glioblastoma stem cells have increased global protein translation, which is achieved via the tRNA modifier YRDC. They show that targeting it or reducing its substrate threonine suppresses tumor growth.
Dobrin et al. develop a fusion receptor comprising the CD80 ectodomain and the 4-1BB cytoplasmic domain, which engages the CD28 and 4-1BB pathways and increases the antitumor potency of HLA-independent (HIT) and TCR-engineered T cells.
Ubhi et al. describe the contribution of APOBEC family members A3C and A3D in the gemcitabine resistance mechanism in the context of pancreatic cancer, which is mediated by facilitating the restart of treatment-induced stalled replication forks.
Ideker and colleagues present NeST-VVN, a deep learning model based on cancer protein assembly data that can be used to predict the response and resistance of cancer cells to CDK4/6 inhibitors.
Subramanian et al. use the EcoTyper machine-learning framework to characterize the tumor, immune and stromal cell states and ecosystems that comprise sarcomas.
Through in vivo tracking of tumor-specific CD8+ T cells in response to immunotherapy in mice, Barboy et al. characterize the tumor response to anti-PD-1 therapy and optimize a combination treatment with anti-4-1BB agonist.
De Blank and colleagues examine data from childhood cancer survivors diagnosed between 1970 and 1999 and find that exposure to radiation decreased over time, and radiation was associated with a higher risk of late mortality and subsequent neoplasms.
Dong et al. demonstrate that targeting arginine N-methyltransferase 9 (PRMT9) inhibits cancer stem cells in the context of acute myeloid leukemia via type I interferon-associated immunity. Furthermore, they show that PRMT9 inhibition synergizes with anti-programmed cell death protein 1.
Roussos-Torres and colleagues perform a phase Ib clinical trial of entinostat, nivolumab and ipilimumab in individuals with advanced HER2-negative breast cancer, report on safety and response and characterize the immune-modulatory effects.
Schmid and colleagues show that pancreatic cancer cell colonization of the liver is accompanied by low-grade tissue injury and efferocytosis, which promotes reprogramming of macrophages and upregulation of arginase.
Benoit and colleagues identify the dopamine transporter antagonist vanoxerine as a suppressor of G9a methyltransferase and show that treatment leads to cancer stem cell suppression and restoration of an immunoresponsive tumor microenvironment in CRC.
Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.