Blockade of CTLA-4 increases anti-tumor response inducing potential of dendritic cell vaccine

Esmaily, Maryam; Masjedi, Ali; Hallaj, Shahin; Nabi‐Afjadi, Mohsen; Malakotikhah, Farinaz; Ghani, Sepideh; Ahmadi, Armin; Sojoodi, Mozhdeh; Hassannia, Hadi; Atyabi, Fatemeh; Namdar, Afshin; Azizi, Gholamreza; Ghalamfarsa, Ghasem; Jadidi‐Niaragh, Farhad

doi:10.1016/j.jconrel.2020.06.017

Cited by 60 publications

(33 citation statements)

References 29 publications

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“…Numerous studies have shown that immune checkpoints are important factors affecting the prognosis and treatment of tumors, including advanced GC [25]. Blocking CTLA4 can enhance the anti-tumor response by promoting the activation of T cells [26]. We hypothesize that immunotherapy can eliminate cancer cells, produce more new antigens, and inhibit the development of tumors, thereby prolonging the life span of patients with advanced GC.…”

Section: Discussionmentioning

confidence: 95%

Comprehensive Analysis and Prognosis Prediction of N6-methyladenosine-related Lncrnas in Immune Microenvironment Infiltration of Gastric Cancer

Huang

Chen

et al. 2021

Preprint

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BackgroundN6-methyladenosine (m6A) RNA modification plays an important role in regulating tumor microenvironment (TME) infiltration. However, the relationship between the expression pattern of m6A-related long non-coding RNAs (lncRNAs) and the immune microenvironment of gastric cancer (GC) is unclear. MethodsIn this study, 23 m6A-related lncRNAs were identified by Pearson’s correlation analysis and univariate Cox regression analysis. According to the expression of these lncRNAs, we identified two distinct molecular clusters by consensus clustering and compared the differences of the TME and enriched pathways between the two clusters. We further constructed a prognostic risk signature and verified it using The Cancer Genome Atlas training and testing cohorts. ResultsThe results showed that cluster 1 was associated with tumor-related and immune activation-related pathways. In addition, cluster 1 was also associated with higher ImmuneScore, StromalScore, and ESTIMATEScore. The results of the stratified survival analysis and independent prognosis analysis indicated that the risk signature is an independent prognostic indicator for patients with GC. In addition, it can effectively predict survival status in patients with different clinical characteristics. Furthermore, our risk model showed that low risk scores were significantly correlated with high expression of programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), as well as sensitivity to chemotherapeutic drugs (e.g., paclitaxel and oxaliplatin). ConclusionsThis evidence contributes to our understanding of the regulation of TME infiltration by m6A-related lncRNAs and my lead to more effective immunotherapy and chemotherapy for patients with GC.

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Section: Discussionmentioning

confidence: 95%

Comprehensive Analysis and Prognosis Prediction of N6-methyladenosine-related Lncrnas in Immune Microenvironment Infiltration of Gastric Cancer

Huang

Chen

et al. 2021

Preprint

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show abstract

“… 25 Blocking CTLA4 can enhance the anti-tumor response by promoting the activation of T cells. 26 We hypothesize that immunotherapy can eliminate cancer cells, produce more new antigens, and inhibit the development of tumors, thereby prolonging the life span of patients with advanced GC. Our results showed that a low-risk score was significantly correlated with high expression of PD-1 and CTLA4, but not PD-L1, LAG3, and IDO1.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis and Prognosis Prediction of N6-Methyladenosine-Related lncRNAs in Immune Microenvironment Infiltration of Gastric Cancer

Huang¹,

Chen²,

Chen³

et al. 2022

IJGM

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Purpose N6-methyladenosine (m6A) RNA modification plays an important role in regulating tumor microenvironment (TME) infiltration. However, the relationship between the expression pattern of m6A-related long non-coding RNAs (lncRNAs) and the immune microenvironment of gastric cancer (GC) is unclear. Methods In this study, 23 m6A-related lncRNAs were identified by Pearson’s correlation analysis and univariate Cox regression analysis. According to the expression of these lncRNAs, we identified two distinct molecular clusters by consensus clustering and compared the differences of the TME and enriched pathways between the two clusters. We further constructed a prognostic risk signature and verified it using The Cancer Genome Atlas training and testing cohorts. Results The results showed that cluster 1 was associated with tumor-related and immune activation-related pathways. In addition, cluster 1 was also associated with higher ImmuneScore, StromalScore, and ESTIMATEScore. The results of the stratified survival analysis and independent prognosis analysis indicated that the risk signature is an independent prognostic indicator for patients with GC. In addition, it can effectively predict survival status in patients with different clinical characteristics. Furthermore, we found that the risk signature was associated with a variety of tumor-infiltrating immune cells, and that low risk scores were significantly correlated with high expression of programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), as well as sensitivity to chemotherapeutic drugs (eg, fluorouracil and oxaliplatin). Conclusion This evidence contributes to our understanding of the regulation of TME infiltration by m6A-related lncRNAs and may lead to more effective immunotherapy and chemotherapy for patients with GC.

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“…In addition, they also fabricated the tumor-lysate-loaded DC vaccine to facilitate priming antitumor T cells. 75 The administration of anti-CTLA-4 siRNA-loaded nanoparticles into CT26 and 4T1 tumor-bearing mice led to the downregulation of CTLA-4 on tumor-infiltrating T cells, which was associated with tumor regression and increased mice survival. Moreover, the administration of DC vaccines in tumor-bearing mice caused mild therapeutic outcomes, and the combination of DC vaccines and siRNA-loaded nanoparticles showed synergistic antitumor effects attributed to the reduction of immunosuppressive cells, improved cytotoxicity of T lymphocytes, decreased inhibitory, and increased inflammatory cytokines, as well as reduced angiogenesis and metastasis processes.…”

Section: Dendritic Cellsmentioning

confidence: 98%

Nanoparticle‐mediated siRNA delivery systems for cancer therapy

Gao

Chen

Santos

2021

VIEW

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The small interfering RNA (siRNA)-based therapeutics have raised great attention since the first RNA interference (RNAi)-derived drug, patisiran, was approved by the US Food and Drug Administration, which represented a landmark in the field of gene therapy. Given the properties of interfering diseaseassociated gene expression, RNAi machinery is regarded as an essential factor for preparing precise medicine. However, over the past few years, siRNA drugs are undergoing a period of clinical translation, in which the major hurdle is the limited efficient delivery strategies. Therefore, this mini-review mainly focuses on describing the state-of-the-art of the nanoscale platforms for delivering siRNA payloads, also addressing their applications in cancer therapy. Finally, the status of siRNA drugs under clinical trials is discussed, providing a comprehensive understanding on the field of oligonucleotide-mediated therapeutics.

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Blockade of CTLA-4 increases anti-tumor response inducing potential of dendritic cell vaccine

Cited by 60 publications

References 29 publications

Comprehensive Analysis and Prognosis Prediction of N6-methyladenosine-related Lncrnas in Immune Microenvironment Infiltration of Gastric Cancer

Comprehensive Analysis and Prognosis Prediction of N6-methyladenosine-related Lncrnas in Immune Microenvironment Infiltration of Gastric Cancer

Comprehensive Analysis and Prognosis Prediction of N6-Methyladenosine-Related lncRNAs in Immune Microenvironment Infiltration of Gastric Cancer

Nanoparticle‐mediated siRNA delivery systems for cancer therapy

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