Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Язык: Английский

---

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Respiratory Research, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 13, 2024

Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.

Язык: Английский

---

FLASH radiotherapy: A new milestone in the field of cancer radiotherapy

Cancer Letters, Год журнала: 2024, Номер 587, С. 216651 - 216651

Опубликована: Фев. 10, 2024

Язык: Английский

---

OTUD4-mediated GSDME deubiquitination enhances radiosensitivity in nasopharyngeal carcinoma by inducing pyroptosis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)

Опубликована: Ноя. 21, 2022

Radioresistance is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure. Previous studies have focused on deficits in cellular apoptosis as a mechanism for radioresistance; however, additional potential death modes involved modulating radiosensitivity NPC not been explored.Pyroptosis was assessed by phase-contrast imaging, LDH release assays, live cell and Western blotting. In vitro vivo assays were used to investigate function gasdermin E (GSDME) ovarian tumor family deubiquitinase 4 (OTUD4). tissues analyzed using blotting, immunohistochemistry, real-time PCR. The molecular determined immunoprecipitation mass spectrometry.Live imaging revealed that 40-75% irradiation-induced dead cells pyroptotic cells. Furthermore, pyroptosis triggered GSDME, which are cleaved activated caspase-3 intrinsic mitochondrial pathway. Additionally, GSDME significantly downregulated radioresistant specimens. Low expression predictor worse prognosis conferred radioresistance both vivo. Mechanistically, OTUD4 deubiquitinated stabilized enhancing promoting pyroptosis. Clinically, correlated with biopsies, patients low suffered worst radiotherapy response survival.GSDME-dependent critical determinant NPC, modulated via deubiquitinating stabilizing GSDME. These findings reveal promising novel direction suggest therapeutic targets sensitizing radiotherapy.

Язык: Английский

---

Development and Validation of a Radiomics Nomogram Using Computed Tomography for Differentiating Immune Checkpoint Inhibitor-Related Pneumonitis From Radiation Pneumonitis for Patients With Non-Small Cell Lung Cancer

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 26, 2022

The combination of immunotherapy and chemoradiotherapy has become the standard therapeutic strategy for patients with unresected locally advance-stage non-small cell lung cancer (NSCLC) induced treatment-related adverse effects, particularly immune checkpoint inhibitor-related pneumonitis (CIP) radiation (RP). aim this study is to differentiate between CIP RP by pretreatment CT radiomics clinical or radiological parameters.A total 126 NSCLC were enrolled in retrospective divided into training dataset (n =88) validation = 38). A 837 features extracted from regions interest based on parenchyma window images. signature was constructed basis predictive least absolute shrinkage selection operator. logistic regression applied develop a nomogram. Receiver operating characteristics curve area under (AUC) evaluate performance etiology identification.There no significant difference datasets any clinicopathological parameters study. signature, named Rad-score, consisting 11 selected features, potential ability empirical α-binormal-based AUCs 0.891 0.896. These results verified AUC 0.901 0.874, respectively. bilateral changes (p < 0.001) sharp border associated identification RP. nomogram model showed good discrimination (AUC 0.953 0.950) 0.947 0.936).CT-based have values differentiating addition produced superior classifying, which could be useful method improve related decision-making.

Язык: Английский

---

Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury

Respiratory Research, Год журнала: 2023, Номер 24(1)

Опубликована: Янв. 24, 2023

Abstract Background Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key solving this problem distinguish between response cells normal epithelial damage. Methods RNA-Seq was used recognize potential target alleviating progression RILI as well inhibiting growth. activation NLRP3 inflammasome screened by qRT-PCR, western blotting, immunofluorescence, ELISA. An vivo model vitro conditioned culture were constructed evaluate effect NLRP3/interleukin-1β on fibroblasts activation. ROS, ATP, (NADP) + /NADP(H) level detected explore mechanism macrophages mice deleted role RILI. Moreover, primary extracted validate results obtained from cell lines. Results after depends glycolysis-related reactive oxygen species accumulation. DPYSL4 activated acts a negative regulator process. triggers interleukin-1β secretion, which directly affects fibroblast activation, proliferation, migration, eventually leading fibrosis. Conclusions Our study suggests that essential for radiation-induced injury. These data strongly indicate targeting may be effective reducing clinical settings.

Язык: Английский

---

Immune checkpoint inhibitor-related pneumonitis: research advances in prediction and management

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 15, 2024

The advent of immune-checkpoint inhibitors (ICIs) has revolutionized the treatment malignant solid tumors in last decade, producing lasting benefits a subset patients. However, unattended excessive immune responses may lead to immune-related adverse events (irAEs). IrAEs can manifest different organs within body, with pulmonary toxicity commonly referred as checkpoint inhibitor-related pneumonitis (CIP). CIP incidence remains high and is anticipated rise further therapeutic indications for ICIs expand encompass wider range malignancies. diagnosis difficult due large individual differences its pathogenesis severity, severe often leads poor prognosis This review summarizes current state clinical research on incidence, risk factors, predictive biomarkers, diagnosis, CIP, we address future directions prevention accurate prediction CIP.

Язык: Английский

---

ACT001 Ameliorates ionizing radiation-induced lung injury by inhibiting NLRP3 inflammasome pathway

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 163, С. 114808 - 114808

Опубликована: Май 3, 2023

Radiotherapy is a prevalent treatment modality for thoracic tumors; however, it can lead to radiation-induced lung injury (RILI), which currently lacks effective interventions. ACT001, prodrug of micheliolide, has demonstrated promising clinical application potential, yet its impact on RILI requires further validation. This study aims investigate the radioprotective effects ACT001 and elucidate underlying mechanism. Sprague-Dawley rats were utilized induce following 20 Gy X-ray chest irradiation, tissue inflammation fibrosis assessed using hematoxylin eosin (H&E) Masson staining. Lung injury, inflammation, oxidative stress markers evaluated employing commercial kits. Pyroptosis-related differentially expressed genes (DEGs) analyzed microarray dataset from Gene Expression Omnibus (GEO) database, their functions hub identified through protein-protein interaction networks. detected via RT-qPCR, western blotting, immunofluorescence, immunohistochemistry. The results that ameliorated RILI, diminished pro-inflammatory cytokine release fibrosis, mitigated activation NLRP3 inflammasome while inhibiting pyroptosis in tissue. In conclusion, our reveals suppress inflammasome-mediated improve suggesting potential as novel protective agent RILI.

Язык: Английский

---

Cellular Atlas of Senescent Lineages in Radiation- or Immunotherapy-Induced Lung Injury by Single-Cell RNA-Sequencing Analysis

International Journal of Radiation Oncology*Biology*Physics, Год журнала: 2023, Номер 116(5), С. 1175 - 1189

Опубликована: Фев. 14, 2023

Although the combination of immunotherapy and radiation therapy to treat various malignancies is rapidly expanding, concerns regarding increased pulmonary toxicities remain. The mechanisms immunotherapy- irradiation-induced lung injury involve a complex interplay cell types signaling pathways, much which remains be elucidated.C57/BL6 mice were treated with single fraction (20 Gy) right or 200 μg anti-Programmed death protein 1 antibody twice week. At 7, 30, 60 days after treatment, tissues obtained for unbiased single-cell RNA sequencing histologic staining. Seurat analysis pipeline, Cellchat, Monocol, Single-Cell rEgulatory Network Inference Clustering used define types, mechanisms, mediators driving pathologic remodeling in response this injury. Reverse transcription polymerase chain reaction, immunofluorescent staining, multiplex immunohistochemistry applied validate key results.Thirty distinct subsets encompassing 75,396 cells identified. A comprehensive investigation cell-cell crosstalk revealed that monokine signals derived from senescent fibroblasts substantially elevated Independent analytical strategies senescence-like subtypes fibroblasts, alveolar epithelial cells, B myeloid immune functionally pathologic, high expression senescence-signature proteins, especially Apolipoprotein E, during response. Senescence markers also irradiated human lines, mouse lines (B3T3 L929), publicly available fibrosis data set.These findings demonstrate accumulation macrophages, primary common mechanism These high-resolution transcriptomic provide novel insights into therapeutic opportunities predict prevent therapy-induced

Язык: Английский

---

Nintedanib-loaded exosomes from adipose-derived stem cells inhibit pulmonary fibrosis induced by bleomycin

Pediatric Research, Год журнала: 2024, Номер 95(6), С. 1543 - 1552

Опубликована: Янв. 20, 2024

Язык: Английский

---