Bioengineered extracellular vesicles presenting PD-L1 and Gal-9 to ameliorate new-onset primary ovarian insufficiency (POI) DOI Creative Commons
Guannan Zhou, Yuanyuan Gu, Jingxin Ding

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract Primary ovarian insufficiency (POI) is a clinical syndrome of dysfunction characterized by premature exhaustion primordial follicles, which causes infertility and dysfunctions many other organ systems including sexuality, bones, the cardiovascular system, neurocognition. An important factor in development POI immune dysregulation, results augmented T cell response ovary. Thus, modulation infiltrated lymphocytes exogenous PD-L1 or Gal-9 an ideal approach for treating POI. Herein, we genetic engineered human umbilical cord mesenchymal stem cells (hucMSCs) derived extracellular vesicles (EVs) overexpressing Gal-9, could restrict activity autoreactive protect from destruction. Moreover, PD-L1-Gal-9 EVs prominently promoted effector apoptosis vitro, reversed decreased AMH mice as well declined proportion CD8+ infiltrating ovaries, contributed to preventing progression preserving residual fertility.

Language: Английский

Co-Occurring Infections in Cancer Patients Treated with Checkpoint Inhibitors Significantly Increase the Risk of Immune-Related Adverse Events DOI Open Access
Siranuysh Grabska, Hovakim Grabski, Tigran Makunts

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2820 - 2820

Published: Aug. 11, 2024

Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal carcinoma, others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode action was found be associated with a broad range immune-related adverse events (irAEs), pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, hepatitis. Depending on their severity, these irAEs often necessitate suspension or discontinuation and, rare instances, may lead fatalities. We analyzed over nineteen million reports identified eighty thousand event from patients treated inhibitors submitted Food Drug Administration's Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, ipilimumab revealed statistically significant association between concurrent infectious diseases for five out seven treatments. Furthermore, trend preserved across all types each individual therapeutic agent cohorts, while remaining two showed same trend, but an increased confidence interval, due insufficient number records.

Language: Английский

Citations

1
Efficacy and safety of PD-1 and PD-L1 inhibitors in advanced colorectal cancer: a meta-analysis of randomized controlled trials DOI Creative Commons

Zhen-Zi Wang,

Yuan Liu, Kedi Wang

et al.

BMC Gastroenterology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 18, 2024

PD-1 and PD-L1 inhibitors have emerged as promising therapies for advanced colorectal cancer (CRC), but their efficacy safety profiles require further evaluation. This meta-analysis aims to assess the of PD-1/PD-L1 in this patient population. A systematic review were conducted following PRISMA guidelines, with data sourced from PubMed, Embase, CENTRAL, Web Science, CNKI up August 3, 2024. Nine randomized controlled trials (RCTs) involving 1680 patients included. The primary outcomes overall survival (OS), progression-free (PFS) objective response rate (ORR), while was assessed through adverse events (AEs) grade ≥ 3 AEs. Effect sizes calculated using mean differences (MD) risk ratios (RR) 95% confidence intervals (CIs). Overall, showed that did not significantly extend OS (MD = 0.86, CI: -0.55, 2.27), they improved PFS 2.53, 0.92, 4.15). Additionally, increase ORR compared controls (RR 1.19, 0.99, 1.44). In terms safety, incidence Subgroup analysis indicated 1.24, 0.20, 2.29) 6.27, 0.56, 11.97), a significant impact on these outcomes. associated higher AEs 1.29, 1.07, 1.57), observed inhibitors. improve CRC, making them preferable option over inhibitors, which show limited severe These findings support prioritizing clinical practice group, caution is warranted due concerns. PROSPERO (CRD42024611696).

Language: Английский

Citations

1
In vitro screening methods of novel immune checkpoint inhibitors related to T cell infiltration and anti-PD-1 resistance DOI

Zhuoying He,

Xiuman Zhou, Youmei Xiao

et al.

Methods in cell biology, Journal Year: 2024, Volume and Issue: unknown, P. 11 - 24

Published: Jan. 1, 2024

Language: Английский

Citations

1
Matairesinol repolarizes M2 macrophages to M1 phenotype to induce apoptosis in triple-negative breast cancer cells DOI

Amol Chaudhary,

Prajakta Patil,

Prerna Raina

et al.

Immunopharmacology and Immunotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: Dec. 26, 2024

Objective Triple-Negative Breast Cancer (TNBC), the most challenging subtype of (BC), currently lacks targeted therapy, presenting a significant therapeutic gap in its management. Tumor Associated Macrophages (TAMs) play role TNBC progression and could be by repolarizing them from M2 to M1 phenotype. Matairesinol (MAT), plant lignan, has been shown exhibit anticancer, anti-inflammatory immunomodulatory activities. In this study, we explored how MAT-induced repolarization THP-1-derived macrophages towards phenotype, which effectively target cell line, MDA-MB-231.

Language: Английский

Citations

1
Bioengineered extracellular vesicles presenting PD-L1 and Gal-9 to ameliorate new-onset primary ovarian insufficiency (POI) DOI Creative Commons
Guannan Zhou, Yuanyuan Gu, Jingxin Ding

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract Primary ovarian insufficiency (POI) is a clinical syndrome of dysfunction characterized by premature exhaustion primordial follicles, which causes infertility and dysfunctions many other organ systems including sexuality, bones, the cardiovascular system, neurocognition. An important factor in development POI immune dysregulation, results augmented T cell response ovary. Thus, modulation infiltrated lymphocytes exogenous PD-L1 or Gal-9 an ideal approach for treating POI. Herein, we genetic engineered human umbilical cord mesenchymal stem cells (hucMSCs) derived extracellular vesicles (EVs) overexpressing Gal-9, could restrict activity autoreactive protect from destruction. Moreover, PD-L1-Gal-9 EVs prominently promoted effector apoptosis vitro, reversed decreased AMH mice as well declined proportion CD8+ infiltrating ovaries, contributed to preventing progression preserving residual fertility.

Language: Английский

Citations

0