Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

X-ray activated platinum complex induces DNA damage and enhances cancer immunotherapy through abscopal effect

ABSTRACT: Radiotherapy is used in more than half of cancer patients, yet most radiosensitisers increase reactive oxygen species (ROS) to enhance cytotoxicity in treated cells. This approach is limited in hypoxic tumours and may cause oxidative injury to healthy tissues. We developed a platinum(II) azido complex (Complex 1) that releases platinonitrene upon X-ray exposure. Platinonitrene reacts with nucleophilic sites on DNA bases, forming covalent adducts that disrupt DNA integrity and cause double-strand breaks, leading to tumour cell death through a mechanism distinct from classical platinum coordination. Computational modelling elucidated this pathway and supported its role in radiosensitisation. Complex 1 was synthesised by sequential ligand exchange of potassium tetrachloroplatinate with cyclohexanediamine, silver nitrate, and sodium azide. In murine models, Complex 1 showed negligible toxicity to major organs and normal immune cells while selectively reducing regulatory T-cell infiltration in tumours. Combined with low-dose radiotherapy and programmed cell death protein 1 blockade, it achieved complete regression of bilateral tumours in forty per cent of mice, demonstrating a strong abscopal effect. This work establishes metallonitrene-based, ROS-independent radiosensitisation for precision radiotherapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE314315 | GEO | 2026/01/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche

Project description:Despite accumulating cases of radiotherapy-induced abscopal effect in the lung cancer with the introduction of immune checkpoint inhibitors (ICIs), the occurrence of this effect remains infrequent and unpredictable to be a therapeutic goal. Here, we showed that the combination of radiotherapy (8Gy*3F) and ICI alleviated the tumor burden at the irradiated site whereas no discernible benefit was observed in the abscopal tumors. RNA-sequencing data showed that extracellular structure organization pathways were enriched in the abscopal tumors after combined therapy, with Sfrp2 being identified as a central hub. SFRP2 expression was observed in cancer-associated fibroblasts (CAFs) and was elevated in abscopal tumors after combined therapy. Blockade of SFRP2 followed by combined radiotherapy and ICI reinvigorated infiltration and cytotoxicity of CD8+ T cells, and elicited regression of abscopal tumors, which was abrogated by CD8α depletion. Mechanistically, in vitro experiments demonstrated that SFRP2+ CAFs induced apoptosis of CD8+ T cells. The spatial transcriptome analysis showed that SFRP2+ CAFs were located in proximity to the vessels and surrounded by abundant macrophages and limited CD8Tex, thereby creating an immunosuppressive perivascular niche, which was validated in paraffin sections of human lung cancer. Lineage-tracing assays showed SFRP2+ CAFs were derived from pericytes. IGF-1 released by irradiated tumors facilitated the transition of pericytes into fibroblasts and stimulated the expression of SFRP2. In summary, SFRP2+ CAFs hijack the abscopal effect from combined radiotherapy and immunotherapy via inducing apoptosis of CD8+ T cells and orchestrating a hostile perivascular niche in the lung cancer. Targeting SFRP2+ CAF may recondition the TME and promote the abscopal effect.

2024-04-01 | GSE261799 | GEO

SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche [B16]

2025-02-06 | GSE283462 | GEO

SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche [II]

2025-02-06 | GSE263386 | GEO

SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche (scRNA-Seq)

2025-02-06 | GSE268525 | GEO

Macrophage-mediated abscopal effects of radiation therapy

Project description:Radiation therapy is a mainstay of cancer treatment, with more than 50% of all cancer patients receiving radiation during the course of their disease. Tumor irradiation can activate both innate and adaptive immune responses, and these responses can be pro- or anti-tumor growth . These observations have led to the search for antitumor approaches combining radiotherapy and specific immunotherapies, most commonly strategies promoting the systemic activation of T cells. Thus far, however, many cancer patients still suffer from local recurrence and/or untreatable metastatic disease after radiotherapy. Here we combine radiotherapy with activation of macrophage-mediated phagocytosis via blockade of the ?don?t-eat-me? cell surface molecule CD47 in small-cell lung cancer (SCLC), a highly metastatic form of lung cancer for which treatment options remain limited. We found that irradiation of SCLC cells in culture results in the secretion of inflammatory cytokines that results in increased migration and phagocytosis by macrophages. In vivo, CD47 blockade potently enhances the local antitumor effects of radiation therapy in murine and human pre-clinical models of SCLC. Strikingly, CD47 blockade also stimulates abscopal antitumor effects inhibiting the growth of non-irradiated SCLC tumors in mice receiving radiation. Similar abscopal antitumor effects were observed in colon cancer and lymphoma models. Surprisingly, these abscopal effects are completely independent of T cells but require macrophages that migrate into the non-irradiated tumor sites in response to inflammatory signals mediated by radiation and are locally activated by CD47 blockade to eliminate cancer cells. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in cancer patients who suffer from metastatic disease.

2022-09-29 | GSE156106 | GEO

X-ray activated platinum complex induces DNA damage and enhances cancer immunotherapy through abscopal effect

Project description:X-ray activated platinum complex induces DNA damage and enhances cancer immunotherapy through abscopal effect

| PRJNA1390704 | ENA

Abscopal Effect for Metastatic Colorectal Cancer

Project description:Patients with colorectal cancer that had metastatic lesions after been treated with definitive surgery or chemoradiotherapy are being asked to participate in this study. 1. To observe immunity-mediated tumor response outside the radiation field (abscopal effect) after chemoradiotherapy of a metastatic site in metastatic colorectal cancer patients. 2. To induce the efficacy (effectiveness) of a new combination of therapy, chemoradiotherapy and thymalfasin for heavily pretreated, metastatic esophageal cancer patients; 3. To explore the role of PET/CT scanning to assess tumor response/abscopal effect. This study will help find out what abscopal effects (good or bad) the combination of radiotherapy and thymalfasin has on metastatic esophageal cancer.

| 2197053 | ecrin-mdr-crc

Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

Project description:Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. To measure the spatiotemporal kinetics of local and abscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and Controltralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.

2023-01-12 | GSE221448 | GEO

Macrophage-mediated abscopal effects of radiation therapy

Project description:Macrophage-mediated abscopal effects of radiation therapy

| PRJNA656781 | ENA

SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche

Project description:SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche

| PRJNA1089112 | ENA