Attempting to Block Cancer's Immune Evasion "Don't Eat Me" Signal in a Course-Based Undergraduate Research Experience

Abstract

In a semester-long Course-based Undergraduate Research
Experience (CURE), 16 students attempted to kill breast cancer cells
by blocking their immune evasion technique. The human breast cancer
cell line MCF-7 upregulates cell surface CD47 to interact with signalregulatory
protein alpha (SIRPα) on THP-1 macrophages to evade
phagocytosis, enabling cancer cell survival. Thrombospondin-1 (TSP1),
a known high-affinity ligand of CD47, was used to outcompete SIRPα
on THP-1 macrophages. By preventing the CD47-SIRPα interaction or
“Don’t eat me” signal, an immune response was expected from THP-
1 macrophages. Interestingly, there did not appear to be phagocytosis
of the MCF-7 cells by THP-1 macrophages but there was a detectable
production of pro-inflammatory cytokine TNFα, compared to controls.
With mixed results, further optimization and experimentation are needed
to confirm the effects of TSP1 on phagocytosis. Further understanding
of ways to manipulate the CD47-SIRPα interaction between cancer and
immune cells could lead to novel combinational immunotherapies.