Determining the effect of a ∆133p53-like isoform on CD4+ T helper cells

Adoptive T cell therapy (ACT) utilizes patient-derived T lymphocytes to target and eliminate tumour cells. While CD8⁺ T cells have been the primary focus of ACT, CD4⁺ T cells have been gaining recognition for their roles in enhancing cytotoxic T lymphocyte (CTL) responses and driving complete tumour regression. However, T cell exhaustion induced by repeated antigen exposure can hinder the success of ACT treatment in solid tumours.

∆133p53, an isoform of the p53 tumour suppressor, has been associated with tumour progression and oncogenic properties. However, previous studies have demonstrated that expression of ∆133p53 in CD8⁺ T cells enhances cellular proliferation, prevents senescence, and downregulates immune checkpoints. These findings suggest that ∆133p53 can improve the anti-tumour efficacy of transferred T cells, particularly in the context of solid tumours. Despite this, the impact of ∆133p53 on CD4⁺ T cell function has yet to be explored.

In this study, we utilized the ∆122p53 isoform as a mouse model of ∆133p53 to compare wild-type (WT) and ∆122p53-expressing CD4⁺ T cells. Key aspects of CD4 T helper 1 (T_H1) cell function were examined, including cellular expansion, surface marker expression, effector cytokine production, and resistance to exhaustion. Based on previous research in CD8⁺ T cells, we hypothesized that ∆122p53 could enhance CD4⁺ T cell function by enhancing proliferative capacity and improving resistance to exhaustion.

Results indicate no influence of ∆122p53 on CD4⁺ T cell function. However, preliminary trends from this study indicate that ∆122p53 may enhance fold expansion and TNF-ɑ production by CD4⁺ T cells. This research contributes to a deeper understanding of ∆133p53’s impact on CD4⁺ T cell function and provides a basis for further research into the therapeutic potential of ∆133p53 in ACT.