Professor Michael Corrin & Dr. Marsela Berstein
Anthracycline is a drug used in cancer chemotherapy. This conceptual illustration depicts one of four hypotheses known regarding the mechanism of anthracycline action. It demonstrates anthracycline triggering translocation of calreticulin from the endoplasmic reticulum to the cell surface of tumour cells. The calreticulin then activates dendritic cells to engulf tumour cells. This project provided experience in: performing a thorough research into an immunological topic using various resources, visualizing cellular environments, visual storytelling, and cell-shading technique. To tell a story with clarity, many iterations were done based on feedback received throughout the process. The assignment was completed in two different formats: schematic two-dimensional and cell-shaded three-dimensional illustrations (the next illustration).
Hypothesis 4: anthracycline triggers translocation of ER-resided calreticulin (CRT) to the cell surface of the dying tumour cells
Figure 4: hypothesis 4 - anthracycline triggers translocation of ER-resided calreticulin (CRT)
1) Tumour cells are treated with anthracycline. 2) 1 hour after treatment, ER-resided calreticulin (CRT) translocates from ER to the cell surface of the dying tumour cell. The cell-surface CRTs release an “eat me” signal. 3) Cell-surface CRT’s “eat me” signal is recognized by (3a) antibodies, which surround CRTs and (3b) C1q and MBP opsonins, which help the interaction between cell-surface CRTs and LRP/CD91 receptors on dendritic cells. This triggers dendritic cells to phagocytose tumour cells. 4) (4a) The engulfed tumour cells release antigens in dendritic cells. (4b) The antigens are also released from free dying tumour cells, and dendritic cells engulf antigens. 5) Dendritic cells carry antigens and enter the regional lymph node through the afferent lymph vessel. In the lymph node, antigens are presented to CD8+, CD4+ T cells and NK cells, and these cells are now activated. 6) Activated CD8+, CD4+ T cells and NK cells exit the lymph node through the efferent lymph vessel and attack and destroy tumour cells.