Abstract
Previous studies identified the p53 isoform, Δ133p53 as an oncogene that promotes cancer
progression and poor prognosis. However, recent research suggests expression of the mouse
analogue, Δ122p53 in tumour cells can enhance a sustained anti-tumour immune response
following adoptive cellular therapy (ACT), while its expression in T cells improves tumour-
specific killing. We aim to investigate how Δ122p53 expression in the tumour and T cells
influences the anti-tumour immune response, hypothesizing that ∆122p53, will stimulate a
durable response, regardless of expression site.
To test this, genetically modified B16-OVA melanoma cells expressing ∆122p53 or an empty
vector (EV) were implanted into mice. Mice were then treated with PBS, wildtype (WT) T cells,
or Δ122p53- expressing T cells to determine therapeutic responses and the ability to inhibit
tumour growth.
Results show that Δ122p53 expression in T cells prolongs stable remission and is associated
with increased CD8+ T cell infiltration in the tumour. Early immune infiltration analysis
suggests that a more robust local immune response may occur three days post-treatment.
Additionally, an endogenous p53 isoform may be induced by ACT treatment.
These findings provide insight into the role of Δ133p53 in shaping the immune response and
could inform strategies to optimize ACT efficacy for solid tumours. The endogenous mouse
ortholog of Δ133p53, ME-Δ123p53, is transcribed from an alternative exon within intron 4 of
the Trp53 gene. This research provides a foundation for future studies to elucidate its role in
modulating the anti-tumour immune response.