Immunotherapies for locally aggressive cancers.

Improving surgical resection outcomes for locally aggressive tumors is key to inducing durable locoregional disease control and preventing progression to metastatic disease. Macroscopically complete resection of the tumor is the standard of care for many cancers, including breast, ovarian, lung, sarcoma, and mesothelioma. Advancements in cancer diagnostics are increasing the number of surgically eligible cases through early detection. Thus, a unique opportunity arises to improve patient outcomes with decreased recurrence rates via intraoperative delivery treatments using local drug delivery strategies after the tumor has been resected. Of the current systemic treatments (e.g., chemotherapy, targeted therapies, and immunotherapies), immunotherapies are the latest approach to offer significant benefits. Intraoperative strategies benefit from direct access to the tumor microenvironment which improves drug uptake to the tumor and simultaneously minimizes the risk of drug entering healthy tissues thereby resulting in fewer or less toxic adverse events. We review the current state of immunotherapy development and discuss the opportunities that intraoperative treatment provides. We conclude by summarizing progress in current research, identifying areas for exploration, and discussing future prospects in sustained remission.

Flexible establishment of functional brain networks supports attentional modulation of unconscious cognition.

In classical theories of attention, unconscious automatic processes are thought to be independent of higher-level attentional influences. Here, we propose that unconscious processing depends on attentional enhancement of task-congruent processing pathways implemented by a dynamic modulation of the functional communication between brain regions. Using functional magnetic resonance imaging, we tested our model with a subliminally primed lexical decision task preceded by an induction task preparing either a semantic or a perceptual task set. Subliminal semantic priming was significantly greater after semantic compared to perceptual induction in ventral occipito-temporal (vOT) and inferior frontal cortex, brain areas known to be involved in semantic processing. The functional connectivity pattern of vOT varied depending on the induction task and successfully predicted the magnitude of behavioral and neural priming. Together, these findings support the proposal that dynamic establishment of functional networks by task sets is an important mechanism in the attentional control of unconscious processing.

Testing the attentional boundary conditions of subliminal semantic priming: the influence of semantic and phonological task sets.

Recent studies challenged the classical notion of automaticity and indicated that even unconscious automatic semantic processing is under attentional control to some extent. In line with our attentional sensitization model, these data suggest that a sensitization of semantic pathways by a semantic task set is necessary for subliminal semantic priming to occur while non-semantic task sets attenuate priming. In the present study, we tested whether masked semantic priming is also reduced by phonological task sets using the previously developed induction task paradigm. This would substantiate the notion that attention to semantics is necessary for eliciting unconscious semantic priming. Participants first performed semantic and phonological induction tasks that should either activate a semantic or a phonological task set. Subsequent to the induction task, a masked prime word, either associated or non-associated with the following lexical decision target word, was presented. Across two experiments, we varied the nature of the phonological induction task (word phonology vs. letter phonology) to assess whether the attentional focus on the entire word vs. single letters modulates subsequent masked semantic priming. In both experiments, subliminal semantic priming was only found subsequent to the semantic induction task, but was attenuated following either phonological induction task. These results indicate that attention to phonology attenuates subsequent semantic processing of unconsciously presented primes whether or not attention is directed to the entire word or to single letters. The present findings therefore substantiate earlier evidence that an attentional orientation toward semantics is necessary for subliminal semantic priming to be elicited.

Attentional sensitization of unconscious visual processing: Top-down influences on masked priming.

Classical theories of automaticity assume that automatic processes elicited by unconscious stimuli are autonomous and independent of higher-level cognitive influences. In contrast to these classical conceptions, we argue that automatic processing depends on attentional amplification of task-congruent processing pathways and propose an attentional sensitization model of unconscious visual processing: According to this model, unconscious visual processing is automatic in the sense that it is initiated without deliberate intention. However, unconscious visual processing is susceptible to attentional top-down control and is only elicited if the cognitive system is configured accordingly. In this article, we describe our attentional sensitization model and review recent evidence demonstrating attentional influences on subliminal priming, a prototypical example of an automatic process. We show that subliminal priming (a) depends on attentional resources, (b) is susceptible to stimulus expectations, (c) is influenced by action intentions, and (d) is modulated by task sets. These data suggest that attention enhances or attenuates unconscious visual processes in congruency with attentional task representations similar to conscious perception. We argue that seemingly paradoxical, hitherto unexplained findings regarding the automaticity of the underlying processes in many cognitive domains can be easily accommodated by our attentional sensitization model. We conclude this review with a discussion of future research questions regar-ding the nature of attentional control of unconscious visual processing.