Mechanisms of T-Cell Exhaustion in Pancreatic Cancer
dc.contributor.author | Saka, Didem | |
dc.contributor.author | Gokalp, Muazzez | |
dc.contributor.author | Piyade, Betul | |
dc.contributor.author | Cevik, Nedim Can | |
dc.contributor.author | Sever, Elif Arik | |
dc.contributor.author | Unutmaz, Derya | |
dc.contributor.author | Ceyhan, Guralp O. | |
dc.contributor.author | Demir, Ihsan Ekin | |
dc.contributor.author | Asimgil, Hande | |
dc.date.accessioned | 2023-02-21T12:34:50Z | |
dc.date.available | 2023-02-21T12:34:50Z | |
dc.date.issued | 2020-01-01 | |
dc.description.abstract | T-cell exhaustion is a phenomenon that represents the dysfunctional state of T cells in chronic infections and cancer and is closely associated with poor prognosis in many cancers. The endogenous T-cell immunity and genetically edited cell therapies (CAR-T) failed to prevent tumor immune evasion. The effector T-cell activity is perturbed by an imbalance between inhibitory and stimulatory signals causing a reprogramming in metabolism and the high levels of multiple inhibitory receptors like programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and Lymphocyte-activation gene 3 (Lag-3). Despite the efforts to neutralize inhibitory receptors by a single agent or combinatorial immune checkpoint inhibitors to boost effector function, PDAC remains unresponsive to these therapies, suggesting that multiple molecular mechanisms play a role in stimulating the exhaustion state of tumor-infiltrating T cells. Recent studies utilizing transcriptomics, mass cytometry, and epigenomics revealed a critical role of Thymocyte selection-associated high mobility group box protein (TOX) genes and TOX-associated pathways, driving T-cell exhaustion in chronic infection and cancer. Here, we will review recently defined molecular, genetic, and cellular factors that drive T-cell exhaustion in PDAC. We will also discuss the effects of available immune checkpoint inhibitors and the latest clinical trials targeting various molecular factors mediating T-cell exhaustion in PDAC. | |
dc.description.issue | 8 | |
dc.description.issue | AUG | |
dc.description.volume | 12 | |
dc.identifier.doi | 10.3390/cancers12082274 | |
dc.identifier.uri | https://hdl.handle.net/11443/1822 | |
dc.identifier.uri | http://dx.doi.org/10.3390/cancers12082274 | |
dc.identifier.wos | WOS:000579052100001 | |
dc.publisher | MDPI | |
dc.relation.ispartof | CANCERS | |
dc.subject | pancreatic ductal adenocarcinoma | |
dc.subject | PDAC | |
dc.subject | T-cell exhaustion | |
dc.subject | epigenetics | |
dc.subject | Thymocyte selection-associated high mobility group box protein | |
dc.subject | TOXs | |
dc.subject | tumor microenvironment | |
dc.subject | TME | |
dc.title | Mechanisms of T-Cell Exhaustion in Pancreatic Cancer | |
dc.type | Article |
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