Ionizing radiation improves skin bacterial dysbiosis in cutaneous T-cell lymphoma.

Introduction: Cutaneous T-cell lymphoma (CTCL) is closely associated with the host microbiome. While recent evidence suggests that shifts in specific bacterial taxa are associated with response to UV-B, a form of non-ionizing radiation, the impact of ionizing radiation (IR) has not been investigated.

Methods: 16S rRNA and gene amplicon sequencing were performed on DNA extracted from swabs of lesional/non-lesional skin of 12 CTCL patients before/after TSEBT or local IR and from 25 matched healthy controls (HC).

N6-methyladenosine reader YTHDF2 in cell state transition and antitumor immunity.

Recent studies revealed that the YTHDF family proteins bind preferentially to the N6-methyladenosine (m6A)-modified mRNA and regulate functions of these RNAs in different cell types. YTHDF2, the first identified m6A reader in mammals, has garnered significant attention because of its profound effect to regulate the m6A epitranscriptome in multiple biological processes. Here, we review current knowledge on the mechanisms by which YTHDF2 exerts its functions and discuss recent advances that underscore the multifaceted role of YTHDF2 in development, stem cell expansion and immune evasion.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

Erratum: Ultrathin Metal-Organic-Layer Mediated Radiotherapy-Radiodynamic Therapy.

[This corrects the article PMC7442115.].

Nanoscale Mixed-Ligand Metal-Organic Framework for X-ray Stimulated Cancer Therapy.

Concurrent localized radiotherapy and systemic chemotherapy are standards of care for many cancers, but these treatment regimens cause severe adverse effects in many patients. Herein, we report the design of a mixed-ligand nanoscale metal-organic framework (nMOF) with the ability to simultaneously enhance radiotherapeutic effects and trigger the release of a potent chemotherapeutic under X-ray irradiation. We synthesized a new functional quaterphenyl dicarboxylate ligand conjugated with SN38 (HQP-SN) via a hydroxyl radical-responsive covalent linkage.

Digitonin-Loaded Nanoscale Metal-Organic Framework for Mitochondria-Targeted Radiotherapy-Radiodynamic Therapy and Disulfidptosis.

The efficacy of radiotherapy (RT) is limited by inefficient X-ray absorption and reactive oxygen species generation, upregulation of immunosuppressive factors, and a reducing tumor microenvironment (TME). Here, the design of a mitochondria-targeted and digitonin (Dig)-loaded nanoscale metal-organic framework, Th-Ir-DBB/Dig, is reported to overcome these limitations and elicit strong antitumor effects upon low-dose X-ray irradiation. Built from ThO(OH) secondary building units (SBUs) and photosensitizing Ir(DBB)(ppy) (Ir-DBB, DBB = 4,4'-di(4-benzoato)-2,2'-bipyridine; ppy = 2-phenylpyridine) ligands, Th-Ir-DBB exhibits strong RT-radiodynamic therapy (RDT) effects via potent radiosensitization with high-Z SBUs for hydroxyl radical generation and efficient excitation of Ir-DBB ligands for singlet oxygen production.

Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment.

Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti-tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME.

Radiotherapy, immunity, and immune checkpoint inhibitors.

Radiotherapy exerts immunostimulatory and immunosuppressive effects, both locally, within the irradiated tumour microenvironment, and systemically, outside the radiation field. Inspired by preclinical data that showed synergy between radiotherapy and immune checkpoint inhibitors, multiple clinical trials were initiated with the hypothesis that combined treatment with radiotherapy and immune checkpoint inhibitors could stimulate a robust systemic immune response and improve clinical outcomes. However, despite early optimism, radioimmunotherapy trials in the curative and metastatic settings have met with little success.

Sharing the Burden: The Case for Definitive Local Therapy in Place of Immune Checkpoint Blockade for Patients With a Low-Volume Burden of Metastatic Disease.

Sharing the burden of low-volume metastatic cancer between ICB and local treatments.

STING activation disrupts tumor vasculature to overcome the EPR limitation and increase drug deposition.

The low success rate of cancer nanomedicines has raised debate on the role of the enhanced permeability and retention (EPR) effect on tumor deposition of nanotherapeutics. Here, we report a bifunctional nanoscale coordination polymer (NCP), oxaliplatin (OX)/2',3'-cyclic guanosine monophosphate-adenosine monophosphate (GA), to overcome the EPR limitation through stimulator of interferon genes (STING) activation and enhance chemotherapeutic and STING agonist delivery for tumor eradication. OX/GA encapsulates GA and OX in the NCP to protect GA from enzymatic degradation and improve GA and OX pharmacokinetics.

Mitochondria-Targeted Multifunctional Nanoparticles Combine Cuproptosis and Programmed Cell Death-1 Downregulation for Cancer Immunotherapy.

The combination of cuproptosis and immune checkpoint inhibition has shown promise in treating malignant tumors. However, it remains a challenge to deliver copper ions and immune checkpoint inhibitors efficiently and simultaneously to tumors. Herein, a mitochondria-targeted nanoscale coordination polymer particle, Cu/TI, comprising Cu(II), and a triphenylphosphonium conjugate of 5-carboxy-8-hydroxyquinoline (TI), for effective cuproptosis induction and programmed cell death-1 (PD-L1) downregulation is reported.

Simultaneous Protonation and Metalation of a Porphyrin Covalent Organic Framework Enhance Photodynamic Therapy.

Covalent organic frameworks (COFs) have been explored for photodynamic therapy (PDT) of cancer, but their antitumor efficacy is limited by excited state quenching and low reactive oxygen species generation efficiency. Herein, we report a simultaneous protonation and metalation strategy to significantly enhance the PDT efficacy of a nanoscale two-dimensional imine-linked porphyrin-COF. The neutral and unmetalated porphyrin-COF (Ptp) and the protonated and metalated porphyrin-COF (Ptp-Fe) were synthesized via imine condensation between 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and terephthalaldehyde in the absence and presence of ferric chloride, respectively.

Radiotherapy and immunology.

The majority of cancer patients receive radiotherapy during the course of treatment, delivered with curative intent for local tumor control or as part of a multimodality regimen aimed at eliminating distant metastasis. A major focus of research has been DNA damage; however, in the past two decades, emphasis has shifted to the important role the immune system plays in radiotherapy-induced anti-tumor effects. Radiotherapy reprograms the tumor microenvironment, triggering DNA and RNA sensing cascades that activate innate immunity and ultimately enhance adaptive immunity.

Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy.

The recent discovery of copper-mediated and mitochondrion-dependent cuproptosis has aroused strong interest in harnessing this novel mechanism of cell death for cancer therapy. Here the design of a core-shell nanoparticle, CuP/Er, for the co-delivery of copper (Cu) and erastin (Er) to cancer cells for synergistic cuproptosis and ferroptosis is reported. The anti-Warburg effect of Er sensitizes tumor cells to Cu-mediated cuproptosis, leading to irreparable mitochondrial damage by depleting glutathione and enhancing lipid peroxidation.

Reconciling the discrepancies in randomized data of combining immunotherapy and radiation therapy: Not all radiotherapy is created equal.

It remains highly unclear and debatable whether combining radiotherapy (RT) and immune checkpoint blocker (ICB) therapy yields improved outcomes compared to either modality alone. Whereas some randomized data have shown improved outcomes, others have not. As a result of these conflicting data, it is essential to reconcile differences in the data and postulate reasons thereof.

Radiotherapy Enhances Metastasis Through Immune Suppression by Inducing PD-L1 and MDSC in Distal Sites.

Purpose: Radiotherapy (RT) is a widely employed anticancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. The purpose of this study is to investigate immune suppressive factors of radiotherapy.

Immunogenic Bifunctional Nanoparticle Suppresses Programmed Cell Death-Ligand 1 in Cancer and Dendritic Cells to Enhance Adaptive Immunity and Chemo-Immunotherapy.

Blockade of programmed cell death-1/programmed cell death-ligand 1 (PD-L1) immune checkpoints with monoclonal antibodies has shown great promise for cancer treatment, but these antibodies can cause immune-related adverse events in normal organs. Here we report a dual-cell targeted chemo-immunotherapeutic nanoscale coordination polymer (NCP), OxPt/BP, comprising oxaliplatin (OxPt) and 2-bromopalmitic acid (BP), for effective downregulation of PD-L1 expression in both cancer cells and dendritic cells (DCs) by inhibiting palmitoyl acyltransferase DHHC3. OxPt/BP efficiently promotes DC maturation by increasing intracellular oxidative stress and enhancing OxPt-induced immunostimulatory immunogenic cancer cell death.

Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy.

Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a two-dimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting.

Corrigendum: Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

[This corrects the article DOI: 10.3389/fmed.2023.

Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

Background: Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions.