Enhanced Immunogenic Cell Death and Antigen Presentation via Engineered Bifidobacterium bifidum to Boost Chemo-immunotherapy DOI

Tingting He,

Lu Wang,

Shuangquan Gou

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(11), P. 9953 - 9971

Published: May 22, 2023

The immunogenic cell death (ICD) of tumor cells has aroused great interest in the field immunotherapy, mainly due to production plentiful tumor-associated antigens (TAAs) and damage-associated molecule patterns. However, doxorubicin (DOX)-induced tumor-specific T-cell-mediated immune response is usually very weak because antigen presentation deficiency immunosuppressive microenvironment (ITME). Herein, probiotic Bifidobacterium bifidum (Bi) was covalently modified with DOX-loaded CaP/SiO2 nanoparticles (DNPs@Bi) for therapy. On one hand, pH-responsive release DOX could induce chemotherapy ICD ITME. other tumor-targeting Bi able significantly enhance TAAs from B16F10 DCs via Cx43-dependent gap junctions. Due combination enhanced presentation, maturation infiltration cytotoxic T lymphocytes ITME were stimulated. As a result, vivo antitumor experiments demonstrated that DNPs@Bi prolonged survival rate inhibited progression metastasis. This strategy bacterial-driven hypoxia-targeting delivery systems offers promising approach chemo-immunotherapy.

Language: Английский

TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance DOI Creative Commons
Xiaoxiao Ma, Shuqin Jia, Gangjian Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 26, 2023

Abstract Immune checkpoint blockade (ICB) offers a new opportunity for treatment gastric cancer (G.C.). Understanding the upstream regulation of immune checkpoints is crucial to further improve efficacy ICB therapy. Herein, using CRISPR-Cas9-based genome-wide screening, we identified TRIM28 as one most significant regulators PD-L1, protein, in G.C. cells. Mechanistically, directly binds and stabilizes PD-L1 by inhibiting ubiquitination promoting SUMOylation. Furthermore, facilitates K63 polyubiquitination TBK1, activating TBK1-IRF1 TBK1-mTOR pathways, resulting enhanced transcription. It was found that positively correlated with Moreover, high expression suggests poor survival cohort 466 patients G.C., this observation consistent while analyzing data from publicly available databases. Ectopic facilitated tumor growth, increased expression, suppressed T cell activation mice. Administration or TBK1 inhibitor significantly alleviated TRIM28-induced progression. combining CTLA4 has synergistic effects on provides novel strategy

Language: Английский

Citations

42
CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors DOI Creative Commons
Lei Peng, Giacomo Sferruzza,

Luojia Yang

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(10), P. 1089 - 1108

Published: Aug. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Language: Английский

Citations

32
Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy DOI Creative Commons
Deepak Chandra Joshi, Anurag Sharma,

Sonima Prasad

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 11, 2024

Novel therapeutic agents in clinical trials offer a paradigm shift the approach to battling this prevalent and destructive disease, area of cancer therapy is on precipice trans formative revolution. Despite importance tried-and-true treatments like surgery, radiation, chemotherapy, disease continues evolve adapt, making new, more potent methods necessary. The field currently witnessing emergence wide range innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, vaccines, utilizes host's immune system selectively target eradicate malignant cells while minimizing harm normal tissue. development targeted medicines kinase inhibitors monoclonal antibodies has allowed for less harmful approaches treating cancer. With help genomics molecular profiling, "precision medicine" customizes therapies each patient's unique genetic makeup maximize efficacy unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, an increasing emphasis combination with synergistic effects further broaden landscape. Multiple-stage are essential determining safety these novel drugs, allowing patients gain access also furthering scientific understanding. future rife promise, as integration artificial intelligence big data potential revolutionize early detection prevention. Collaboration among researchers, healthcare providers, active involvement remain bedrock ongoing battle against In conclusion, dynamic evolving landscape provides hope improved treatment outcomes, emphasizing patient-centered, data-driven, ethically grounded we collectively strive towards cancer-free world.

Language: Английский

Citations

24
Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study DOI Creative Commons
Hanmei Lou, Hongbing Cai, Xin Huang

et al.

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(8), P. 1501 - 1508

Published: Feb. 19, 2024

Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, bispecific antibody targeting PD-1 CTLA-4, plus standard therapy first-line R/M CC (recurrent and/or metastatic cancer).

Language: Английский

Citations

18
The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial DOI Creative Commons

Da Xu,

Hongwei Wang, Qun Ma

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

This open-label phase II trial (NCT04542837) aimed to evaluate the efficacy and safety of KN046 combined with lenvatinib in patients advanced hepatocellular carcinoma (HCC), explore potential response biomarkers. Participants received 5 mg/kg every 3 weeks 12 or 8 mg once daily. The primary endpoints were safety, tolerability, dose-limiting toxicity (DLT), objective rate (ORR) according RECIST v1.1. A total fifty-five participants enrolled. results meet pre-specified endpoints. No DLT was observed run-in period. incidence serious adverse events grade ≥3 treatment-related (TRAEs) 30.9% 47.3%, respectively. Grade immunotherapy-related occurred (5.5%) participants. Five (9.1%) discontinued treatment due TRAEs, all which 1-2. ORR 45.5% (95% CI, 31.97-59.45). median progression-free survival 11.0 8.21-15.24) months. overall (OS) 16.4 11.20-not estimable) months, 12-month OS 60.0% 45.87-71.55). Circulating tumor DNA status before third cycle associated prognosis. In conclusion, First-line plus shows promising for unresectable metastatic HCC.

Language: Английский

Citations

4
New insight in immunotherapy and combine therapy in colorectal cancer DOI Creative Commons
Kai Ji,

Hang Jia,

Zixuan Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 7, 2025

The advent of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) treatment marks a major breakthrough. These therapies have proven safer and more effective than traditional radiotherapy targeted treatments. Immunotherapies like pembrolizumab, nivolumab, ipilimumab pioneered new avenues, potentially improving patient outcomes quality life. Additionally, advances immunotherapy prompted detailed research into CRC therapies, especially those integrating ICIs with conventional treatments, providing hope for patients shaping future practice. This review delves the mechanisms various evaluates their therapeutic potential when combined radiotherapy, chemotherapy, clinical settings. It also sheds light on current application involving treatment.

Language: Английский

Citations

2
Pan-cancer and experimental analyses reveal the immunotherapeutic significance of CST2 and its association with stomach adenocarcinoma proliferation and metastasis DOI Creative Commons
Dan Huang, Jing Li,

Zhijun He

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 24, 2025

Purpose Cystatin 2 (CST2) is a cysteine protease inhibitor, and recent research suggests its potential involvement in cancer development. However, role the occurrence, progression, prognosis of pan-cancer has not been systematically investigated. Materials methods This study comprehensively analyzes differential expression CST2 pan-cancer. The distribution patterns were examined using single-cell datasets. Furthermore, we conducted comprehensive evaluation correlation between various factors. These factors include prognosis, immune cell infiltration, immune-related genes, mutations, methylation, tumor mutation burden (TMB), microsatellite instability (MSI). In addition, analyzed sensitivity drugs dependent on expression. We utilized gene set enrichment analysis (GSEA) to explore biological functions across different types. Finally, gastric lines, will investigate impact knockout levels, clonal proliferation, apoptosis, migration. Results exhibits abnormal overexpression multiple tumors. Single-cell reveals high fibroblasts. closely associated with TMB, MSI. Enrichment demonstrated significant pathways. stomach adenocarcinoma (STAD), CST2-related risk models are demonstrate strong predictive capabilities, while also being linked microenvironment. Drug indicates 21 chemotherapy drugs. experimental validation revealed significantly elevated STAD, indicating as driver regulating malignant proliferation Conclusion serves biomarker, playing critical facilitating migration processes STAD.

Language: Английский

Citations

2
CircRHBDD1 augments metabolic rewiring and restricts immunotherapy efficacy via m6A modification in hepatocellular carcinoma DOI Creative Commons
Juan Cai, Zhiqiang Chen, Yao Zhang

et al.

Molecular Therapy — Oncolytics, Journal Year: 2022, Volume and Issue: 24, P. 755 - 771

Published: Feb. 22, 2022

Circular RNAs are a class of highly conserved with stable covalently closed circular structures. Metabolic reprogramming cancer cells reshapes the tumor microenvironment and can suppress antitumor immunity. Here, we discovered novel RNA, termed circRHBDD1, which augments aerobic glycolysis restricts anti-PD-1 therapy in hepatocellular carcinoma (HCC). Mechanistic studies revealed that circRHBDD1 recruits m6A reader YTHDF1 to PIK3R1 mRNA accelerates translation an m6A-dependent manner. EIF4A3-mediated exon back-splicing contributes upregulation circRHBDD1. Moreover, is expressed responder HCC patients, targeting improves immune-competent mouse model. Overall, these findings illustrate metabolic importance circRHBDD1/YTHDF1/PIK3R1 axis show suppression may bolster efficacy for treatment.

Language: Английский

Citations

67
Machine learning-based tumor-infiltrating immune cell-associated lncRNAs for predicting prognosis and immunotherapy response in patients with glioblastoma DOI
Hao Zhang, Nan Zhang,

Wantao Wu

et al.

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 23(6)

Published: Aug. 24, 2022

Abstract Long noncoding ribonucleic acids (RNAs; lncRNAs) have been associated with cancer immunity regulation. However, the roles of immune cell-specific lncRNAs in glioblastoma (GBM) remain largely unknown. In this study, a novel computational framework was constructed to screen tumor-infiltrating cell-associated (TIIClnc) for developing TIIClnc signature by integratively analyzing transcriptome data purified cells, GBM cell lines and bulk tissues using six machine learning algorithms. As result, could distinguish survival outcomes patients across four independent datasets, including Xiangya in-house dataset, more importantly, showed superior performance than 95 previously established signatures gliomas. revealed be an indicator infiltration level cells predicted response immunotherapy. The positive correlation between CD8, PD-1 PD-L1 verified dataset. newly demonstrated predictive biomarker, enabled precise selection population who would benefit from immunotherapy should validated applied near future.

Language: Английский

Citations

67
Visual Analysis of Colorectal Cancer Immunotherapy: A Bibliometric Analysis From 2012 to 2021 DOI Creative Commons

Long Ma,

Jixiang Ma,

Muzhou Teng

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 31, 2022

An increasing number of studies have shown that immunotherapy serves a significant role in treating colorectal cancer (CRC) and has become hotspot. However, few used the bibliometric method to analyze this field comprehensively. This study collected 1,899 records CRC from 2012 October 31, 2021, CiteSpace regions, institutions, journals, authors, keywords predict latest trends research. The United States China, contributing more than 60% publications, were main drivers field. Sun Yat-sen University was most active institution, while National Cancer Institute had highest frequency citations. Most publications published Journal for Immunotherapy Cancer. Adam E Snook prolific writer, Dung T. Le commonly co-cited author. “T cell”, “MMI” “PD-1blocked” widely studied aspects immunotherapy. “Immune checkpoint inhibitor”, “combination therapy”, “drug therapy” “liver metastases” current research hotspots. “Tumor microenvironment”, “neutrophils”, “tumor-associated macrophages”, “suppressor cell” emerged as hotspots recent years. “Gut microbiota”, “nanoparticle” “tumor mutational burden” recently frontiers should be closely monitored.

Language: Английский

Citations

56