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Sievers, B.

Publications and source records attributed to Sievers, B..

3 recordsLinked to original sources

Spatiotemporal dynamics of adoptively transferred stem-like CD8+ T cells in the tumor microenvironment following vaccination

Adoptive cell therapy (ACT) of tumor-specific T cells can improve survival in a subset of cancer patients. Current ACT approaches may be limited by using highly differentiated T cells which can be inhibited by an immunosuppressive tumor microenvironment (TME). Here, we developed an approach to optimize ACT and used spatial transcriptomics to show how stem-like and effector CD8+ T cells differentially mediate tumor control following vaccination. Spatial transcriptomic profiling of the TME showed that ACT with stem-like T cells followed by intravenous vaccination prevented immune exclusion, increased infiltration of pro-inflammatory macrophages, and reprogrammed tumor cells to upregulate Type I and Type II IFN signaling and apoptotic gene programs. The protective transcriptomic signature of the TME in this ACT model contained overlapping biomarkers with patients who responded to ACT therapy. This approach demonstrates synergy between transferred stem-like T cells and intravenous vaccination to transcriptionally remodel the TME and enhance tumor control.

immunology↗

SAMPL: The Spreading Activation and Memory PLasticity Model

We present the Spreading Activation and Memory PLasticity Model (SAMPL), a computational model of how memory retrieval changes memories. SAMPL restructures memory networks as a function of spreading activation and plasticity. Memory networks are represented as graphs of items in which edge weights capture the strength of association between items. When an item is retrieved, activation spreads across nodes depending on edge weights and the strength of initial activation. A non-monotonic plasticity rule, in turn, updates edge weights following activation. SAMPL simulates human memory phenomena across a number of experiments including retrieval induced forgetting, context-based memory enhancement, and memory synchronization in conversational networks. Our results have implications for theorizing memory disorders such as PTSD and designing computationally assisted conversational therapy.

animal behavior and cognition↗

Visual and auditory brain areas share a neural code for perceived emotion

Emotionally expressive music and dance occur together across the world. This may be because features shared across the senses are represented the same way even in different sensory brain areas, putting music and movement in directly comparable terms. These shared representations may arise from a general need to identify environmentally relevant combinations of sensory features, particularly those that communicate emotion. To test the hypothesis that visual and auditory brain areas share a representational structure, we created music and animation stimuli with crossmodally matched features expressing a range of emotions. Participants confirmed that each emotion corresponded to a set of features shared across music and movement. A subset of participants viewed both music and animation during brain scanning, revealing that representations in auditory and visual brain areas were similar to one another. This shared representation captured not only simple stimulus features, but also combinations of features associated with emotion judgments. The posterior superior temporal cortex represented both music and movement using this same structure, suggesting supramodal abstraction of sensory content. Further exploratory analysis revealed that early visual cortex used this shared representational structure even when stimuli were presented auditorily. We propose that crossmodally shared representations support mutually reinforcing dynamics across auditory and visual brain areas, facilitating crossmodal comparison. These shared representations may help explain why emotions are so readily perceived and why some dynamic emotional expressions can generalize across cultural contexts.

neuroscience↗