Perforin: A Key Pore-Forming Protein for Immune Control of Viruses and Cancer

Thiery, Jérôme; Lieberman, Judy

doi:10.1007/978-94-017-8881-6_10

Cited by 50 publications

(52 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Soluble tumor antigens from tumor cells are captured by antigen presenting cells (APCs), and then combined with major histocompatibility complex (MHC) class I molecules into complex which expressed on APCs. The T cell receptors (TCRs) recognize the complex and then promote the activation of CTLs which kill tumor cells by releasing perforin or promoting apoptosis [6, 43]. These previous studies were consistent with our results which showed that high level of CD8+ TILs correlated with better survival in EC in general.…”

Section: Discussionsupporting

confidence: 82%

“…CD4 + T cells can promote the proliferation and differentiation of immune cells, and coordinate the interaction between immune cells [5]. CD8 + T cells are the main antitumor effector cells that kill tumor cells by releasing perforin or promoting apoptosis [6]. CD57 is involved in the killing effect of activated natural killer (NK) cells and closely related to the expression of cytotoxins such as granzyme and perforin [7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8⁺ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3⁺ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57⁺ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3⁺, CD4⁺ and CD45RO⁺ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…This was a larger percentage compared with the value reported in a previous study (39), where a value of 16.6% CD8 + T lymphocytes was reported for an autologous lysate-based vaccine, which was considered to be clinically successful. The strong statistical correlation between the mean survival time and CD8a + population size in the present study (r= 0.985) indicates that cytotoxic T-lymphocytes may be a pivotal element in the vaccine-induced antitumour immune response, which is in agreement with data from the literature (40)(41)(42)(43)(44).…”

Section: Discussionsupporting

confidence: 92%

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

et al. 2018

View full text Add to dashboard Cite

Abstract. Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a Bacillus subtilis protein fraction as an adjuvant. Median and overall survival, size of metastatic foci in lung tissue and levels of circulating CD8a + T cells were evaluated and compared with untreated control mice. Following primary tumour removal, a course of three subcutaneous vaccinations with xenogeneic chicken embryo vaccine led to significant increase in overall survival rate (100% after 70 days of follow-up vs. 40% in untreated control mice), significant increase in circulating CD8a + T cells (18.18 vs. 12.6% in untreated control mice), and a significant decrease in the area and incidence of metastasis foci. The xenogeneic rat brain tissue-based vaccine did not improve any of the investigated parameters, despite promising reports in other models. We hypothesize that the proper selection of antigen source (tissue) can constitute an effective immunotherapeutic product.

show abstract

“…The granule mediators of target cell lysis are serine proteases, known as granzymes (Gzms), which induce programmed cell death (2-4) after they are delivered into the target cell cytoplasm by the pore-forming protein perforin (PFN) (5)(6)(7).…”

mentioning

confidence: 99%

Granzyme B–Activated p53 Interacts with Bcl-2 To Promote Cytotoxic Lymphocyte–Mediated Apoptosis

Safta

Ziani

Favre

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Granzyme B (GzmB) plays a major role in CTLs and NK cell–mediated elimination of virus-infected cells and tumors. Human GzmB preferentially induces target cell apoptosis by cleaving the proapoptotic Bcl-2 family member Bid, which, together with Bax, induces mitochondrial outer membrane permeabilization. We previously showed that GzmB also induces a rapid accumulation of the tumor-suppressor protein p53 within target cells, which seems to be involved in GzmB-induced apoptosis. In this article, we show that GzmB-activated p53 accumulates on target cell mitochondria and interacts with Bcl-2. This interaction prevents Bcl-2 inhibitory effect on both Bax and GzmB-truncated Bid, and promotes GzmB-induced mitochondrial outer membrane permeabilization. Consequently, blocking p53–Bcl-2 interaction decreases GzmB-induced Bax activation, cytochrome c release from mitochondria, and subsequent effector caspases activation leading to a decreased sensitivity of target cells to both GzmB and CTL/NK-mediated cell death. Together, our results define p53 as a new important player in the GzmB apoptotic signaling pathway and in CTL/NK-induced apoptosis.

show abstract

Perforin: A Key Pore-Forming Protein for Immune Control of Viruses and Cancer

Cited by 50 publications

References 116 publications

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

Granzyme B–Activated p53 Interacts with Bcl-2 To Promote Cytotoxic Lymphocyte–Mediated Apoptosis

Contact Info

Product

Resources

About