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Figure S7 from γδ T Cells Support Antigen-Specific αβ T cell–Mediated Antitumor Responses during BCG Treatment for Bladder Cancer

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posted on 2023-04-04, 01:22 authored by Niannian Ji, Neelam Mukherjee, Zhen-Ju Shu, Ryan M. Reyes, Joshua J. Meeks, David J. McConkey, Jonathan A. Gelfond, Tyler J. Curiel, Robert S. Svatek

Figure S7 - Figure.S7 shows combination of rapamycin and BCG increase absolute number of human effector memory γδ T cells expanded in vitro and reduce the growth of patient-derived xenograft bladder cancer cells in vivo.

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ARTICLE ABSTRACT

Bacillus Calmette-Guérin (BCG) is the most effective intravesical agent at reducing recurrence for patients with high-grade, non–muscle-invasive bladder cancer. Nevertheless, response to BCG is variable and strategies to boost BCG efficacy have not materialized. Prior work demonstrated a requirement for either conventional αβ or nonconventional γδ T cells in mediating BCG treatment efficacy, yet the importance of T-cell antigen specificity for BCG's treatment effect is unclear. Here, we provide direct evidence to show that BCG increases the number of tumor antigen–specific αβ T cells in patients with bladder cancer and protects mice from subsequent same-tumor challenge, supporting BCG induction of tumor-specific memory and protection. Adoptive T-cell transfers of antigen-specific αβ T cells into immunodeficient mice challenged with syngeneic MB49 bladder tumors showed that both tumor and BCG antigen–specific αβ T cells contributed to BCG efficacy. BCG-specific antitumor immunity, however, also required nonconventional γδ T cells. Prior work shows that the mTOR inhibitor rapamycin induces the proliferation and effector function of γδ T cells. Here, rapamycin increased BCG efficacy against both mouse and human bladder cancer in vivo in a γδ T cell–dependent manner. Thus, γδ T cells augment antitumor adaptive immune effects of BCG and support rapamycin as a promising approach to boost BCG efficacy in the treatment of non–muscle-invasive bladder cancer.

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