Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of nave or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from nave or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of nave cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their nave or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy.
Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity.
Specimen part
View SamplesComparative analysis of cerebellar gene expression changes occurring in Sca1154Q/2Q and Sca7266Q/5Q knock-in mice
The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7.
Sex, Age
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Anchorage-independent cell growth signature identifies tumors with metastatic potential.
Specimen part, Cell line
View SamplesCultured cancer cells exhibit substantial phenotypic heterogeneity when measured in a variety of ways such as sensitivity to drugs or the capacity to grow under various conditions. Among these, the ability to exhibit anchorage-independent cell growth (colony forming capacity in semisolid media) has been considered to be fundamental in cancer biology because it has been connected with tumor cell aggressiveness in vivo such as tumorigenic and metastatic potentials, and also utilized as a marker for in vitro transformation. Although multiple genetic factors for anchorage-independence have been identified, the molecular basis for this capacity is still largely unknown. To investigate the molecular mechanisms underlying anchorage-independent cell growth, we have used genome-wide DNA microarray studies to develop an expression signature associated with this phenotype. Using this signature, we identify a program of activated mitochondrial biogenesis associated with the phenotype of anchorage-independent growth and importantly, we demonstrate that this phenotype predicts potential for metastasis in primary breast and lung tumors.
Anchorage-independent cell growth signature identifies tumors with metastatic potential.
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