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Biology subjects

Wicker, B.

Publications and source records attributed to Wicker, B..

3 recordsLinked to original sources

Label-Free In-Line Characterization of Immune Cell Culture using Quantitative Phase Imaging

Cell therapies, including T cell immunotherapies, offer promising treatments for previously untreatable diseases, but their widespread use is hindered by challenges in monitoring therapeutic cells during culture--impacting consistency, potency, and cost. This work demonstrates the use of quantitative phase imaging (QPI), specifically a compact, non-interferometric form called quantitative oblique back illumination microscopy (qOBM), for non-destructive, label-free, in-line assessment of T cell cultures. qOBM enables near real-time feedback on culture growth, contamination, and cell status (viability and activation), comparable to flow cytometry. We further apply this method to characterize genetically modified CAR T cells and explore its potential for advanced T cell phenotyping. Analysis of data from over 50 independent donors shows strong correlation between qOBM metrics and traditional destructive at-line assays. Overall, qOBM provides a powerful tool for continuous, in-line monitoring of therapeutic cell cultures, which can be transformative for improving reproducibility, reducing costs, and advancing the development of cell-based therapies.

immunology↗

Disseminating cells in human tumours acquire an EMT stem cell state that is predictive of metastasis

Cancer stem cells (CSCs) undergo epithelial-mesenchymal transition (EMT) to drive metastatic dissemination in experimental cancer models. However, tumour cells undergoing EMT have not been observed disseminating into the tissue surrounding human tumour specimens, leaving the relevance to human cancer uncertain. We have previously identified both EpCAM and CD24 as markers of EMT CSCs with enhanced plasticity. This afforded the opportunity to investigate whether retention of EpCAM and CD24 alongside upregulation of the EMT marker Vimentin can identify disseminating EMT CSCs in human tumours. Examining disseminating tumour cells in over 12,000 imaging fields from 84 human oral cancer specimens, we see a significant enrichment of single EpCAM, CD24 and Vimentin co-stained cells disseminating beyond the tumour body in metastatic specimens. Through training an artificial neural network, these predict metastasis with high accuracy (cross-validated accuracy of 87-89%). In this study, we have observed single disseminating EMT CSCs in human oral cancer specimens, and these are highly predictive of metastatic disease.

cancer biology↗

Real-world expectations and their affective value modulate object processing

It is well known that expectations influence how we perceive the world. Yet the neural mechanisms underlying this process remain unclear. Studies about the effects of prior expectations have focused so far on artificial contingencies between simple neutral cues and events. Real-world expectations are however often generated from complex associations between contexts and objects learned over a lifetime. Additionally, these expectations may contain some affective value and recent proposals present conflicting hypotheses about the mechanisms underlying affect in predictions. In this study, we used fMRI to investigate how object processing is influenced by realistic context-based expectations, and how affect impacts these expectations. First, we show that the precuneus, the inferotemporal cortex and the frontal cortex are more active during object recognition when expectations have been elicited a priori, irrespectively of their validity or their affective intensity. This result supports previous hypotheses according to which these brain areas integrate contextual expectations with object sensory information. Notably, these brain areas are different from those responsible for simultaneous context-object interactions, dissociating the two processes. Then, we show that early visual areas, on the contrary, are more active during object recognition when no prior expectation has been elicited by a context. Lastly, BOLD activity was shown to be enhanced in early visual areas when objects are less expected, but only when contexts are neutral; the reverse effect is observed when contexts are affective. This result supports the proposal that affect modulates the weighting of sensory information during predictions. Together, our results help elucidate the neural mechanisms of real-world expectations.

neuroscience↗