Cover ImageTreatment with a PD-L1–specific antibody can lead to durable responses across several cancer types. Limitations to such treatment include not all patients responding to these therapeutics and some that do respond developing immune-related adverse events. Petit et al. show that targeted delivery of PD-L1 blockade to tumors using tumor-targeting CD8+ T cells engineered to secrete an anti–PD-L1 nanobody has greater therapeutic efficacy in mouse models than systemic administration of PD-L1–specific antibody. The local delivery of anti–PD-L1 nanobody improved PD-L1 blocking at the tumor site and avoided systemic exposure, suggesting that this approach might overcome limitations to treatment with PD-L1–specific antibody. Read more in this issue on page 713. Original image from Fig. 5C. Artwork by Lewis Long.Close Modal
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Cancer Immunology Research (2013-Present)(ISSN 2326-6066) Published monthly since 2013.
Cancer Immunity (2001-2013; volumes 1-13)(EISSN 1424-9634) Published periodically from 2001-2013.
Table of Contents
What We're Reading
A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors
In the Spotlight
Revival and Recharacterization of a Preclinical Model of Hormone-Dependent Breast Cancer to Study Immunotherapy
Cancer Immunology at the Crossroads
Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer
Carcinogen-induced rat mammary tumors are shown to recapitulate many aspects of human breast cancer, including the immune environment. Tumor growth is associated with immune escape, which can be reversed by immunotherapy, highlighting the potential utility of this model.
Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
Maximizing bispecific T-cell engager (BiTE) efficacy in solid tumors is challenging. Here, key requirements for BiTE efficacy are identified, including tumor diffusion, target expression level, lymphoid tissue involvement, and DC-driven responses, highlighting possible strategies to improve this therapy.
T Cell–Mediated Targeted Delivery of Anti–PD-L1 Nanobody Overcomes Poor Antibody Penetration and Improves PD-L1 Blocking at the Tumor Site
Local anti–PD-L1 nanobody delivery by tumor-specific T cells increases therapeutic efficacy and reduces systemic exposure compared to systemic injection of PD-L1–specific antibody. Poor intratumoral penetration of PD-L1–specific antibody is a factor limiting efficacy in vivo.
Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma
In the first ten patients treated with a combination immunotherapy comprising a neoantigen-loaded dendritic cell vaccine and neoantigen-activated T cells, those who had a neoantigen-specific immune response had improved disease-free survival, supporting continuation of the phase II trial.
Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients
This study demonstrates the efficacy of an engineered oncolytic Vaccinia virus (Pexa-Vec) in patients with metastatic cancers. A single intravenous infusion associates with tumor necrosis, IFNα secretion and chemokine expression, and transient innate and long-lived adaptive antitumor responses.
Targeting WEE1/AKT Restores p53-Dependent Natural Killer–Cell Activation to Induce Immune Checkpoint Blockade Responses in “Cold” Melanoma
Treatment of immune checkpoint blockade (ICB)-resistant preclinical melanoma models with WEE1 and AKT inhibitors promotes tumor immune infiltration and induces ICB responses. The data suggest that similar approaches in humans could enhance the clinical utility of ICB drugs.
Circadian Regulator CLOCK Drives Immunosuppression in Glioblastoma
The minimal responsiveness of glioblastoma to immunotherapy is partly due to robust infiltration of immune-suppressive microglia. Inhibition of the CLOCK–OLFML3–HIF1α–LGMN axis reduces microglial infiltration and immune-suppressive polarization, increases antitumor immunity, and enhances immunotherapy efficiency.