Testudinidosis: A New Mechanism of Resistance to Immune Attack
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471716 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Antibody dependent cell-mediated cytotoxicity (ADCC) provides a model for uncovering immune resistance mechanisms. We continuously exposed epidermal growth factor receptor (EGFR)+ A431 cells to KIR-deficient NK92-CD16V effector cells and the anti-EGFR mAb cetuximab. Persistent ADCC exposure yielded ADCC-resistant cells (ADCCR1) that, compared with control ADCC-sensitive cells (ADCCS1), exhibited reduced EGFR expression, overexpression of histone- and interferon-related genes and failure to activate NK cells, without evidence of epithelial: mesenchymal transition. These properties gradually reversed following withdrawal of ADCC selection pressure. A second A431-derived ADCC-resistant cell line maintained EGFR expression. Remarkably, ADCCR1 cells possessed lower expression of multiple cell surface molecules that contribute to cell: cell interactions and immune synapse formation. Classic immune checkpoints did not modulate ADCC in this unique model system of immune resistance. Just as giant tortoises (Testudinidae) can hide in their shells to avoid predation, this novel immune evasion mechanism, termed testudinidosis, can protect cells against immune attack.
2021-05-16 | GSE114545 | GEO
Project description:RNA-seq and ATAC-seq of tumor resistance to immune cell attack
| PRJNA836528 | ENA
Project description:Validation of AS1 as novel regulator of tumor resistance to immune cell attack
| PRJNA408285 | ENA
Project description:Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that work by targeting molecules on immune cells that can inhibit the immune system's ability to attack cancer cells. One such checkpoint molecule is PD-1, which is found on the surface of T cells (a type of immune cell) and helps to prevent them from attacking healthy cells. When PD-1 binds to its ligand (a molecule on the surface of some cells), it sends a signal to the T cell to \\"turn off\\" and not attack the cell. This mechanism is important in preventing the immune system from attacking healthy cells, but it can also be exploited by cancer cells to avoid detection and destruction by the immune system. In this study YUMM2.1 mouse tumour cells were implanted subcutaneously. The effect of IFN-γ-pre-treatment, PARP14 inhibition and PD-1 antibody treatment are reported by RNA-seq.
2023-08-22 | E-MTAB-12872 | biostudies-arrayexpress
Project description:Establishing the genetic map of primary and secondary resistance of Chinese wild RAS colorectal cancer received anti-EGFR treatment through tissues and peripheral blood NGS testing. Combination genetic data with clinical characteristics, prognosis and treatment data to explore the molecular mechanism of resistance of anti-EGFR-antibody.
| 2345214 | ecrin-mdr-crc
Project description:A novel antibiotic resistance mechanism
| PRJEB25942 | ENA
Project description:Targeted monoclonal antibody therapy is a promising therapeutic strategy for cancer, and antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial mechanism underlying these approaches. The majority of patients have limited responses to monoclonal antibody therapy due to the development of resistance. Models of ADCC provide a system for uncovering immune-resistance mechanisms. We continuously exposed epidermal growth factor receptor (EGFR+) A431 cells to KIR-deficient NK92-CD16V effector cells and the anti-EGFR cetuximab. Persistent ADCC exposure yielded ADCC-resistant cells (ADCCR1) that, compared with control ADCC-sensitive cells (ADCCS1), exhibited reduced EGFR expression, overexpression of histone- and interferon-related genes, and a failure to activate NK cells, without evidence of epithelial-to-mesenchymal transition. These properties gradually reversed following withdrawal of ADCC selection pressure. The development of resistance was associated with lower expression of multiple cell-surface molecules that contribute to cell-cell interactions and immune synapse formation. Classic immune checkpoints did not modulate ADCC in this unique model system of immune resistance. We showed that the induction of ADCC resistance involves genetic and epigenetic changes that lead to a general loss of target cell adhesion properties that are required for the establishment of an immune synapse, killer cell activation, and target cell cytotoxicity.
| S-EPMC6359950 | biostudies-literature
Project description:In spite of the remarkable clinical benefit from immune checkpoint blockade in melanoma, both intrinsic and acquired resistance prevent durable clinical responses in many patients. Whereas melanomas are known to acquire MART-1 T cell resistance by reversible phenotype switching to an NGFRhi state, less is known about mechanisms of intrinsic immune resistance. To mimic recurrent T cell attack, we chronically exposed a panel of (patient-derived) melanoma cell lines to clinically relevant MART-1 differentiation antigen-specific cytotoxic T cells. This led to strong enrichment of a pre-existing cell population that exhibited immune resistance in vitro and in mice. These fractions showed high expression of NGFR, were maintained stably, and were found to be present in patients’ melanomas prior to treatment. Remarkably, these NGFRhi melanoma cells also displayed resistance also to T cells recognizing antigens that are unrelated to melanoma differentiation. Furthermore, these cells exhibited multidrug-resistance to other therapies including BRAF + MEK inhibition, suggesting that they exist in a stable and distinct cellular state. Clinically corroborating these findings, a tumor-intrinsic NGFR signature predicted aPD-1 therapy resistance, while NGFRhi melanoma fractions in patients were associated with immune exclusion. Lastly, genetic or pharmacologic NGFR inhibition restored tumor sensitivity to T cell attack in vitro and in melanoma xenografts. These findings demonstrate the existence of a stable and pre-existing NGFRhi multitherapy-refractory melanoma subpopulation, which ought to be eliminated to revert intrinsic resistance to immunotherapeutic intervention.
2020-07-02 | GSE147091 | GEO
Project description:Here, we investigate therapy-induced senescence (TIS) as a reversible mechanism of drug resistance in breast cancer cells. High-dose doxorubicin treatment was used to induce TIS in four distinct breast cancer cell lines and the drug resistance/sensitivity pattern of parental and TIS cells were investigated using a panel of FDA-approved anticancer molecules.
Proteome analysis confirmed the presence of the Senescence-Associated Secretory Phenotype (SASP), altered spliceosomal activity and proteins with significant role in immune evasion.
2024-11-19 | PXD058028 | JPOST Repository
Project description:Two wild house mice lines were genetically selected for short and long attack latency. Mice with an attack latency <50s or >600s were considered short attack latency mice (SAL) and long attack latency mice(LAL) respectively. RNA from the hippocampus of 14 SAL or 14 LAL mice was pooled and used as input material for the SAGE libraries. Keywords: other
2003-10-31 | GSE786 | GEO