Enhanced systemic antitumor efficacy of PD‐1/PD‐L1 blockade with immunological response induced by photodynamic therapy DOI Creative Commons
Takumi Sonokawa, Yukio Fujiwara, Cheng Pan

et al.

Thoracic Cancer, Journal Year: 2024, Volume and Issue: 15(18), P. 1429 - 1436

Published: May 13, 2024

Abstract Background Photodynamic therapy (PDT) is an antitumor and has traditionally been regarded as a localized in itself. However, recent reports have shown that it not only exerts direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized the immunological response induced by PDT could potentially enhance efficacy of programmed death‐1 (PD‐1) / death‐ligand 1 (PD‐L1) blockade. Methods The effects colon 26 were investigated vitro using WST assay. whether anti‐PD‐1 antibodies be amplified addition PDT. performed combination randomly allocating tumor‐bearing mice to four treatment groups: control, antibodies, PDT, To analyze microenvironment after treatment, tumors resected pathologically evaluated. Results viability rate decreased proportionally with laser dose. In vivo experiments for combined antibody showed enhanced compared control. Immunohistochemical findings 10 days indicated number CD8+ cells, area Iba‐1+ expressing PD‐L1 significantly higher treated than alone, or Conclusions increased immune cell infiltration into microenvironment. may PD‐1/PD‐L1

Language: Английский

Bladder sparing options for muscle-invasive bladder cancer DOI

Ekaterina Laukhtina,

Marco Moschini, Jeremy Yuen‐Chun Teoh

et al.

Current Opinion in Urology, Journal Year: 2024, Volume and Issue: 34(6), P. 471 - 476

Published: Sept. 2, 2024

This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview future directions field.

Language: Английский

Citations

2
Blockade of CD73 potentiates radiotherapy antitumor immunity and abscopal effects via STING pathway DOI Creative Commons
Ran An, Chao Wu,

Cunyu Tang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 16, 2024

Abstract Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, upregulated after RT and associated with poor prognosis in CRC patients. This study aims elucidate the mechanisms driving RT-induced CD73 upregulation investigate how combining blockade stimulates immune responses induces abscopal effects. Findings revealed that mediated by ataxia telangiectasia Rad3-related (ATR) pathway correlated tolerance, as demonstrated through flow cytometry, immunofluorescence, Western Blotting. Using cytometry multicolor experiments subcutaneous tumor models, combination therapy reduces infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T (Tregs) while increasing dendritic (DCs) CD8 + cells, resulting superior responses. Additionally, results from Blot, RNA sequencing enhances antigen-presenting ability DCs activates antigen-specific improving their function delaying depletion. The activation cGAS-STING IFN-I pathways this effect. In summary, integration effectively reverses immunosuppressive TME invigorates cell-driven, specific These insights shed fresh light on governing synergistic modulation immunity CRC, offering promising avenues advancement therapeutic strategies against CRC.

Language: Английский

Citations

2
Bidirectional regulation of the cGAS-STING pathway in the immunosuppressive tumor microenvironment and its association with immunotherapy DOI Creative Commons
Yurui Zhang, Yudi Wang,

Peizheng Mu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 11, 2024

Adaptive anti-tumor immunity is currently dependent on the natural immune system of body. The emergence tumor immunotherapy has improved prognosis and prolonged survival cycle patients. Current mainstream immunotherapies, including checkpoint blockade, chimeric antigen receptor T-cell immunotherapy, monoclonal antibody therapy, are linked to immunity. cGAS-STING pathway an important signaling that plays role in fighting against invasion foreign pathogens maintaining homeostasis organism. Increasing evidence suggests a key immunity, combination STING-related agonists can significantly enhance efficacy reduce immunotherapeutic resistance. However, double-edged sword, its activation immunosuppression. Immunosuppressive cells, M2 macrophages, MDSC, regulatory T microenvironment play crucial escape, thereby affecting effect. bi-directionally regulate this group immunosuppressive targeting affect function providing new ideas for immunotherapy. In study, we summarize immunological elaborate escape mediated by microenvironment. Finally, approaches related explore ways improve them, guidelines further clinical services.

Language: Английский

Citations

1
A Facile and Promising Delivery Platform for siRNA to Solid Tumors DOI Creative Commons

Qixin Leng,

Aishwarya Anand,

A. James Mixson

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5541 - 5541

Published: Nov. 23, 2024

Over 20 years have passed since siRNA was brought to the public's attention. Silencing genes with has been used for various purposes, from creating pest-resistant plants treating human diseases. In last six years, several therapies approved by FDA, which solely target disease-inducing proteins in liver. The extrahepatic utility of systemically delivered primarily limited preclinical studies. While targeting liver comprises relatively simple ligand-siRNA conjugates, diseases such as cancer often requires complex carriers. complexity these carriers reduces likelihood their widespread clinical use. current report, we initially demonstrated that a linear histidine-lysine (HK) carrier siRNA, injected intravenously, effectively silenced luciferase expressed MDA-MB-435 tumors mouse model. This non-pegylated peptide easily synthesized compared cRGD-conjugated pegylated branched peptides our group previously. Notably, tumor-targeting component, KHHK, embedded within peptide, eliminating need conjugate ligand carrier. Moreover, brief bath sonication significantly improved vitro and vivo silencing HK polyplexes. Several other containing -KHHK- sequence were then screened some 80% tumor marker. Additionally, polyplexes confirmed second Not only activity reduced, but also reduced Raf-1 oncogene MDA-MB-231 xenografts. These simple-to-synthesize, effective, are promising

Language: Английский

Citations

1
Enhanced systemic antitumor efficacy of PD‐1/PD‐L1 blockade with immunological response induced by photodynamic therapy DOI Creative Commons
Takumi Sonokawa, Yukio Fujiwara, Cheng Pan

et al.

Thoracic Cancer, Journal Year: 2024, Volume and Issue: 15(18), P. 1429 - 1436

Published: May 13, 2024

Abstract Background Photodynamic therapy (PDT) is an antitumor and has traditionally been regarded as a localized in itself. However, recent reports have shown that it not only exerts direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized the immunological response induced by PDT could potentially enhance efficacy of programmed death‐1 (PD‐1) / death‐ligand 1 (PD‐L1) blockade. Methods The effects colon 26 were investigated vitro using WST assay. whether anti‐PD‐1 antibodies be amplified addition PDT. performed combination randomly allocating tumor‐bearing mice to four treatment groups: control, antibodies, PDT, To analyze microenvironment after treatment, tumors resected pathologically evaluated. Results viability rate decreased proportionally with laser dose. In vivo experiments for combined antibody showed enhanced compared control. Immunohistochemical findings 10 days indicated number CD8+ cells, area Iba‐1+ expressing PD‐L1 significantly higher treated than alone, or Conclusions increased immune cell infiltration into microenvironment. may PD‐1/PD‐L1

Language: Английский

Citations

1