Study of the Neural Basis for Subjective Feature Binding

While it is known that the brain perceives color and motion asynchronously, the specific locations in which the brain binds signals remain unknown. This study distinguishes subjective perception of the capability to bind features and the objective accuracy in feature binding. The stimuli were the same for individual subjects, consisting of random dots (red and green, or yellow and blue) moving either vertically or horizontally. Subjects responded to questions regarding the color or the direction of motion of the dots (objective judgment) and rated their capability in performing the task (subjective judgment). The imaging results of contrasting subjective judgment showed that the activation of the anterior rostral cingulate cortex (rACC) and inferior frontal gyrus (Brodmann area [BA] 45/47) during incapable-of-binding responses, compared with the capable-of-binding responses. It is suggested that the rACC is for uncertainty of subjective judgment and BA 45/47 is for the increased burden on working memory. In contrast, there was no imaging results of contrasting the correct and incorrect responses (i.e., objective judgment), and neither was there for the interaction between subjective and objective judgment. The results of conservative conjunction analysis indicated common and shared brain areas for the 2 distinctive binding situations (the correct and capable-of-binding vs the incorrect and incapable-of-binding), including increased activity in the intraparietal lobe (IPL) and the junction areas of the posterior rostral ACC (dACC) and the prefrontal areas, but decreased activity in the medial portion of the IPL, suggesting that feature binding requires maintaining attention. These results clearly isolated subjective judgment from objective judgment and support the view that maintaining attention is involved in feature binding of color and motion.

Activation of phagocytosis by immune checkpoint blockade

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-a （SIRPa）, on tumor-associated macrophages （TAMs） and its cognate ligand cluster of differentiation 47 （CD47） on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 （PD-1） in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.

A Novel mRNA Signature Related to Immunity to Predict Survival and Immunotherapy Response in Hepatocellular Carcinoma

Background and Aims:Hepatocellular carcinoma(HCC)is the most common primary liver cancer and the incidence and mortality rates are increasing.Given the limited treatments of HCC and promising application of immunotherapy for cancer,we aimed to identify an immune-related prognostic signature that can predict overall survival(OS)rates and immunotherapy response in HCC.Methods:The initial signature development was conducted using a training dataset from the Cancer Genome Atlas followed by independent internal and external validations from that resource and the Gene Expression Omnibus.A signature based nomogram was generated using multivariate Cox regression analysis.The associations of signature score with tumor immune phenotype and response to immunotherapy were analyzed using single-sample gene set enrichment analysis and tumor immune dysfunction and exclusion algorithm.A cohort from Zhongshan Hospital was employed to verify the pre dictive robustness of the signature regarding prognostic risk and immunotherapy response.Results:The prognostic signature,IGS_(HCC),consisting of 22 immune-related genes,had independent prognostic ability,with training and validation cohorts.Also,IGS_(HCC)stratified HCC patients with different outcomes in subgroups.The prognostic accuracy of IGS_(HCC)was better than three reported prognostic signatures.The IGS_(HCC)-based nomogram had high accuracy and significant clinical benefits in predicting 3-and 5-year OS.IGS_(HCC)reflected distinct immunosuppressive phenotypes in low-and high-score groups.Patients with low IGS_(HCC)scores were more likely than those with high scores to benefit from immunotherapy.Conclusions:IGS_(HCC)predicted HCC prognosis and response to immunotherapy,and contributed to individualized clinical management.