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Title
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2B4 IS A CHECKPOINT MOLECULE FOR iNKT CELL ANTI-TUMOR RESPONSE
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Creator
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Bahal, Devika Naresh
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Date
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2022
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Collection
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Electronic Theses & Dissertations
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Description
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Invariant natural killer T (iNKT) cells are robust cytotoxic effectors and immune modulators, which makes them ideal candidates for cancer immunotherapy. However, the use of iNKTs for cellular therapy against cancer has been limited due to their transient response in pre-clinical trials. Although TCR-CD1d interactions are generally required for iNKT cell cytotoxicity, the receptors and signaling mechanisms that co-operate with the TCR to promote maximal anti-tumor responses are poorly...
Show moreInvariant natural killer T (iNKT) cells are robust cytotoxic effectors and immune modulators, which makes them ideal candidates for cancer immunotherapy. However, the use of iNKTs for cellular therapy against cancer has been limited due to their transient response in pre-clinical trials. Although TCR-CD1d interactions are generally required for iNKT cell cytotoxicity, the receptors and signaling mechanisms that co-operate with the TCR to promote maximal anti-tumor responses are poorly understood. Therefore, elucidating the mechanisms that regulate anti-tumor responses is critical for the development of effective iNKT-based therapies. Our efforts have shown that 2B4, a SLAM receptor, when expressed on iNKTs reduces their cytotoxic response against lymphoma cells. Surprisingly, 2B4 is not expressed on resting iNKTs but gets rapidly upregulated via stimulation through the TCR. 2B4 has two isoforms, which are splice variants of each other, of which the inhibitory long form is predominantly expressed in activated iNKTs. Our data show that 2B4 is a checkpoint molecule and has an inhibitory role in iNKT cell cytotoxicity. Indeed, when we overexpressed 2B4 in an iNKT cell hybridoma, the killing capacity of the iNKT cell line was abrogated. Moreover, 2B4 can be converted to a potent activating receptor by swapping its intracellular domains with proline motifs, which drastically augments tumor cell lysis. Taken together, this study highlights the important role of 2B4 in iNKT cell cytolysis and broadens the knowledge of immunoregulatory receptors in iNKT cells for future applications in cancer therapy.
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Title
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"You got a little bit of everything in you" : narration as resistance in Corregidora and Eva's Man
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Creator
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Rann, Christina Ann
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Date
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2016
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Collection
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Electronic Theses & Dissertations
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Description
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Narrative has the power to construct worlds both fictional and real—to carve out spaces for marginalized voices, to engage in the most intimately human conversations, and to open up new possibilities for expression and resistance. The narrative worlds Gayl Jones constructs in Corregidora and Eva’s Man betray “linearity, logic, and conventional realism,” as Trimiko Melancon states (140), in order to challenge our thinking about racialized gender discourses taken up in the law, the economy, and...
Show moreNarrative has the power to construct worlds both fictional and real—to carve out spaces for marginalized voices, to engage in the most intimately human conversations, and to open up new possibilities for expression and resistance. The narrative worlds Gayl Jones constructs in Corregidora and Eva’s Man betray “linearity, logic, and conventional realism,” as Trimiko Melancon states (140), in order to challenge our thinking about racialized gender discourses taken up in the law, the economy, and in literary representation. Using “unnatural” narratology—a theory that has attempted to grapple with postmodern texts such as Jones’s—as a mooring point, this project intends to explore how Jones uses disruptive narrative practices to write up against the boundaries of stereotype and positivist representations of black subjectivities. By radically shifting how she tells her protagonists’ stories, Jones invites her readers to question the many oppressive forces that shape Corregidora and Eva’s Man while giving her protagonists a way to resist these forces with the power of their own voices, or lack thereof.
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