Authors:

Viren Maira

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About Paper:

The BCL-2 family of proteins regulates the intrinsic mitochondrial pathway of apoptosis by balancing pro- and anti-apoptotic signals that determine cell survival or death. Beyond apoptosis, these proteins also play important immunomodulatory roles. The LaBelle Lab has shown that BH3 mimetics, which inhibit anti-apoptotic BCL-2 family proteins, enhance the tumor-killing capacity of expanding chimeric antigen receptor (CAR) T cells. However, the regulation and dynamics of BCL-2 family proteins during T cell expansion remain poorly understood. To address this gap, we characterized BCL-2 family protein expression in healthy human T cells during ex vivo expansion. Flow cytometry analyses revealed consistent temporal shifts in protein expression, with levels increasing during early activation, peaking, and subsequently declining. This pattern was observed across both pro- and anti-apoptotic proteins in helper and cytotoxic T cell subsets. In contrast, RT-qPCR analyses showed variable transcriptional trends, suggesting that transcription is not the dominant regulatory mechanism controlling BCL-2 family protein expression. Ongoing studies are validating these findings by Western blot and will examine how BH3 mimetics alter BCL-2 family expression, transcription, and protein interactions. These findings provide insight into the dynamic regulation of BCL-2 family proteins during T cell expansion and may inform strategies to modulate immune cell function and improve the efficacy of immunotherapies.

Source:

University of Chicago

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Co-authors:

Viren Maira