Davis, K. C. | Search bioRxiv

bioRxiv2021

A Pan-Cancer Census of Dominant Tumor Immune Archetypes

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations and other features of the surrounding tissue. It is likely that persistent tumors differentially engage inherent patterns-here Archetypes-of the immune system, to both benefit from a tumor immune microenvironment (TIME) and to disengage tumor-targeting. To discover dominant immune system archetypes, the Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub compartments uncovered archetypes that exist across indications. These Immune composition-based archetypes differentiate tumors based upon unique immune and tumor gene-expression patterns. Archetypes discovered this way also tie closely to well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune infiltration and provides a rational path forward to learn how to modulate these patterns to improve therapy. O_FIG O_LINKSMALLFIG WIDTH=182 HEIGHT=200 SRC="FIGDIR/small/441344v1_ufig1.gif" ALT="Figure 1"> View larger version (77K): org.highwire.dtl.DTLVardef@55a5ccorg.highwire.dtl.DTLVardef@f8205corg.highwire.dtl.DTLVardef@1480b8org.highwire.dtl.DTLVardef@eb94e_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Differences in Chemo-signaling Compound-Evoked Brain Activity in Male and Female Young Adults: A Pilot Study in the Role of Sexual Dimorphism in Olfactory Chemo-Signaling

IntroductionPrevious studies have shown that putative pheromones 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST) cause activation in the preoptic area/anterior hypothalamus in men and women. Sex differences in neural activation patterns have been demonstrated when participants are subject to pheromone stimulation; however, whether other compounds give rise to similar neural activity has not been completely investigated. MethodsTwenty-nine young adults [16 female (21.3+/-0.54; mean yrs+/-SE), 13 male (22.85+/-0.42)] participated in a 3-block design, where participants were exposed to a scent (lavender), a synthetic male pheromone (4,16-androstadien-3b-ol; ALD), and a synthetic female pheromone (1,3,5(10),16-Estratetraen-3-ol; EST) via an automated olfactometer. Whole-brain, high-resolution (1.8mm3) functional MRI data from a Siemens Trio 3T MRI scanner were collected during all blocks. Five adults were excluded due to excessive movement. MANOVA analysis, a 2 x 3 multivariate model and analysis of 2x2 effects between sex and subsets of stimuli was done for activation over the whole brain and small volumes involved in olfaction. ResultsExploratory analysis of 2x2 effects between sex and subsets of stimuli exhibited significant interactions when assessing activations over the whole brain, and small volumes involved in olfaction. The left and right frontal poles (LFP, RFP) shows significant interaction when assessing sex with lavender and EST for whole brain analysis. For small volume analysis, the right orbitofrontal cortex (ROFC) exhibited a sex with lavender and ALD interaction, and a sex with lavender and EST interaction was observed in the left inferior frontal gyrus (LIFG). Main effects of sex, stimulus, or interaction show no differences analyzed using a 2 x 3 multivariate model. ConclusionThe study shows there is a sexually dimorphic response in the olfactory system to pheromones not previously studied. Scents like lavender do not have this same response. These distinct functional differences in activation patterns may be a result of neural development and maturation differences between sexes. Future studies should expand this pilot study and involve a younger demographic to accurately determine the age at which the olfactory response differentiates between males and females.

neuroscience↗