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Background <p>Cancer is a leading cause of mortality worldwide, necessitating the development of novel therapeutic targets and strategies to prevent recurrence and metastasis. In this study, we aimed to evaluate whether a recombinant attenuated <i>Salmonella</i> vaccine (RASV) can stimulate antitumor immunity and prevent cancer progression in vivo.</p> Methods <p>We established a mouse model by transplanting cancer cells subcutaneously 4&#xa0;weeks after oral RASV inoculation and analyzed bone marrow (BM) cells and tumor-infiltrated immune cells by flow cytometry. Further, we established a 4&#xa0;T-1-induced metastatic cancer model to evaluate the RASV-mediated prevention of tumor metastasis.</p> Results <p>Adjuvant RASV significantly reduced tumor growth by enhancing CD8<sup>+</sup> T cell activity and inducing changes in BM progenitor cells, which contributed combinatorically to the antitumor effects of RASV by increasing the number of common lymphoid progenitor cells. The antitumor effects mediated by RASV were inhibited upon interleukin (IL)-7 receptor blockage. Moreover, interferon-γ-stimulated genes, including <i>Irf1</i>, were upregulated in the BM of RASV-treated mice, thus mediating IL-7 expression. Furthermore, RASV inoculation prevented lung metastasis in mice with breast cancer.</p> Conclusions <p>RASV inoculation can promote marked alterations in the BM microenvironment, thus reshaping the anticancer immune response in vivo. This strategy holds therapeutic potential for preventing cancer recurrence and metastasis.</p> Graphical abstract <p></p>

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Recombinant attenuated Salmonella vaccine promotes CD8+ T cell-dependent antitumor immunity via IFN-γ-induced IRF-1-mediated upregulation of IL-7

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Jae-Hyeon Jeong,
  • Dae-Joon Kim,
  • Chae-Won Kim,
  • Youngjoo Han,
  • Ah-Ra Jang,
  • Jong-Hwan Park,
  • Nara Tae,
  • Jae-Hee Ahn,
  • Jaewon Cho,
  • Sun Shim Choi,
  • Mi-Na Kweon,
  • Dae Hee Kim,
  • Hyun-Jeong Ko

摘要

Background

Cancer is a leading cause of mortality worldwide, necessitating the development of novel therapeutic targets and strategies to prevent recurrence and metastasis. In this study, we aimed to evaluate whether a recombinant attenuated Salmonella vaccine (RASV) can stimulate antitumor immunity and prevent cancer progression in vivo.

Methods

We established a mouse model by transplanting cancer cells subcutaneously 4 weeks after oral RASV inoculation and analyzed bone marrow (BM) cells and tumor-infiltrated immune cells by flow cytometry. Further, we established a 4 T-1-induced metastatic cancer model to evaluate the RASV-mediated prevention of tumor metastasis.

Results

Adjuvant RASV significantly reduced tumor growth by enhancing CD8+ T cell activity and inducing changes in BM progenitor cells, which contributed combinatorically to the antitumor effects of RASV by increasing the number of common lymphoid progenitor cells. The antitumor effects mediated by RASV were inhibited upon interleukin (IL)-7 receptor blockage. Moreover, interferon-γ-stimulated genes, including Irf1, were upregulated in the BM of RASV-treated mice, thus mediating IL-7 expression. Furthermore, RASV inoculation prevented lung metastasis in mice with breast cancer.

Conclusions

RASV inoculation can promote marked alterations in the BM microenvironment, thus reshaping the anticancer immune response in vivo. This strategy holds therapeutic potential for preventing cancer recurrence and metastasis.

Graphical abstract