Cell death induced by the Fas/Fas ligand pathway and its role in pathology

Waring, Paul; Müllbacher, Arno

doi:10.1046/j.1440-1711.1999.00837.x

Cited by 263 publications

(180 citation statements)

References 83 publications

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“…Interleukin-10 (encoded by the IL10 gene) is an immunosuppressive cytokine known to inhibit tumor-specific type 1 immune responses. 41 Fas ligand (FASLG) promotes activation-induced cell death (AICD) of activated T and B cells 42 and is believed to confer immune privilege to tumors by inducing apoptosis in tumor infiltrating lymphocytes. 43 Serpin Family C Member 1 (SERPINC1), also known as Antithrombin III, is a known inhibitor of T cell-derived Granzyme A.…”

Section: Discussionmentioning

confidence: 99%

Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

et al. 2018

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Mounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). Tumor immune subclasses were associated with survival in patients with high TMB (TMB-Hi, P < 0.001) but not in those with low TMB (TMB-Lo, P = 0.44). This statistical relationship was confirmed in the METABRIC cohort (TMB-Hi, P = 0.047; TMB-Lo, P = 0.39), and also found to hold true in the more-indolent Luminal A tumor subtype (TMB-Hi, P = 0.011; TMB-Lo, P = 0.91). In TMB-Hi tumors, the FID subclass was associated with prolonged survival independent of tumor stage, molecular subtype, age and treatment. Copy number analysis revealed the reproducible, preferential amplification of chromosome 1q immune-regulatory genes in the PID immune subclass. These findings demonstrate a previously unappreciated role for TMB as a determinant of immune-mediated survival of breast cancer patients and identify candidate immune-regulatory mechanisms associated with immunologically cold tumors. Immune subtyping of breast cancers may offer opportunities for therapeutic stratification.

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Section: Discussionmentioning

confidence: 99%

Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

et al. 2018

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“…This process plays a very important role in immune homeostasis [34,35]. There are many factors involved in the AICD.…”

Section: Discussionmentioning

confidence: 99%

Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45β

Wang

Cao

et al. 2006

Cell Res

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Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57Bl/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P<0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD45b was measured by real-time PCR. The results indicated that GADD45b transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/Bl mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P<0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.

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“…P53 has been reported to upregulate the pro-apoptotic Bax protein and downregulate the anti-apoptotic Bcl-2 protein Selvakumaran et al, 1994;Miyashita and Reed, 1995;Findley et al, 1997). The apoptotic signal death receptor CD95 (Fas) is induced by p53 increasing sensitivity to apoptosis signals (Morimoto et al, 1993;Owen-Schaub et al, 1995;Muller et al, 1998;Waring and Mullbacher, 1999). The majority of evidence indicates that transcriptional regulation of proteins associated with apoptosis is the primary way p53 induces apoptosis.…”

Section: Apoptosis Versus Necrosismentioning

confidence: 99%

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

Holmes¹,

Soprano²,

Soprano³

2004

Journal Cellular Physiology

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Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR.

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Cell death induced by the Fas/Fas ligand pathway and its role in pathology

Cited by 263 publications

References 83 publications

Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45β

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

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