ABSTRACT
The tumor microenvironment (TME) and the cellular interactions within it can be critical to tumor progression and treatment response. Although technologies to generate multiplex images of the TME are advancing, the many ways in which TME imaging data can be mined to elucidate cellular interactions are only beginning to be realized. Here, we present a novel approach for multipronged computational immune synapse analysis (CISA) that reveals T-cell synaptic interactions from multiplex images. CISA enables automated discovery and quantification of immune synapse interactions based on the localization of proteins on cell membranes. We first demonstrate the ability of CISA to detect T-cell:APC (antigen presenting cell) synaptic interactions in two independent human melanoma imaging mass cytometry (IMC) tissue microarray datasets. We then generate melanoma histocytometry whole slide images and verify that CISA can detect similar interactions across data modalities. Interestingly, CISA histoctyometry analysis also reveals that T-cell:macrophage synapse formation is associated with T-cell proliferation. We next show the generality of CISA by extending it to breast cancer IMC images, finding that CISA quantifications of T-cell:B-cell synapses are predictive of improved patient survival. Our work demonstrates the biological and clinical significance of spatially resolving cell-cell synaptic interactions in the TME and provides a robust method to do so across imaging modalities and cancer types.
ABSTRACT
Psychologists and counselors completed a questionnaire devised by the authors to explore the relationships between their extent of endorsement of empathy definitions, their use and views of empathy, and their identification with theories of psychotherapy. Results from 565 respondents suggested that those who identified with humanistic/experiential and psychodynamic theories seemed to have similar views of how empathy is defined and viewed and reported that they use empathy more than those with other theoretical inclinations. These findings suggest that there is some consistency between theoretical identification and definition, as well as reported use and views of empathy.