De Carvalho, F. | Search bioRxiv

bioRxiv2025

Tumor B cell infiltration in platinum-treated advanced urothelial carcinoma

Platinum-based chemotherapy combined with immunotherapy provides durable disease control in advanced urothelial cancer. However, cisplatin and carboplatin differently impact the tumor immune microenvironment, affecting chemo-immunotherapy response. Here, we evaluate immune cell populations and ecosystems associated with overall survival in patients treated with platinum-based chemotherapy. Our transcriptomic analysis of pretreatment tumor samples from three cohorts (189 patients) of advanced urothelial cancer showed that lymphoid cell infiltration was significantly associated with prolonged overall survival. In cisplatin-treated patients, high memory B cell infiltration provided a significant overall survival improvement, but no such association was found in carboplatin-treated patients. Additionally, gene expression signatures implicated in B cell memory lineage and associated cytokines were associated with better overall survival in independent cancer patient cohorts. Our findings highlight memory B cell infiltration as a potential prognostic biomarker in urothelial cancer and emphasize the role of the tumor immune microenvironment in chemotherapy response.

cancer biology↗

bioRxiv2022

Conserved population dynamics in the cerebro-cerebellar system between waking and sleep

Despite the importance of the cerebellum for motor learning, and the recognised role of sleep in motor memory consolidation, surprisingly little is known about activity in the sleeping cerebro-cerebellar system. Here we used wireless recording from M1 and the cerebellum in monkeys to examine the relationship between patterns of single-unit spiking activity observed during waking behaviour and in natural sleep. Across the population of recorded units, we observed similarities in the timing of firing relative to local field potential features associated with both movements during waking and up-states during sleep. We also observed a consistent pattern of asymmetry in pair-wise cross-correlograms, indicative of preserved sequential firing in both wake and sleep at low frequencies. Despite the overall similarity in population dynamics between wake and sleep, there was a global change in the timing of cerebellar activity relative to motor cortex, from contemporaneous in the awake state, to motor cortex preceding the cerebellum in sleep. We speculate that similar population dynamics in waking and sleep may imply that cerebellar internal models are activated in both states, but that their output is decoupled from motor cortex in sleep. Nevertheless, spindle frequency coherence between the cerebellum and motor cortex may provide a mechanism for cerebellar computations to influence sleep-dependent learning processes in the cortex. Significance statementIt is well known that sleep can lead to improved motor performance. One possibility is that synaptic changes during sleep result from off-line repetitions of neuronal activity patterns in brain areas responsible for the control of movement. In this study we show for the first time that neuronal patterns in the cerebro-cerebellar system are conserved during both movements and sleep up-states, albeit with a shift in the relative timing between areas. Additionally, we show the presence of simultaneous M1-cerebellar spike coherence at spindle frequencies associated with up-state replay and postulate that this is a mechanism whereby a cerebellar internal models can shape plasticity in neocortical circuits during sleep.

neuroscience↗