Bacteria colonization in tumor microenvironment creates a favorable niche for immunogenic chemotherapy

See Khai Lim, Wen Ching Lin, Sin Wei Huang, Yi Chung Pan, Che Wei Hu, Chung Yuan Mou, Che Ming Jack Hu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The tumor microenvironment (TME) presents differential selective pressure (DSP) that favors the growth of cancer cells, and monovalent therapy is often inadequate in reversing the cancer cell dominance in the TME. In this work, we introduce bacteria as a foreign species to the TME and explore combinatorial treatment strategies to alter DSP for tumor eradication. We show that cancer-selective chemotherapeutic agents and fasting can provide a strong selection pressure against tumor growth in the presence of bacteria. Moreover, we show that an immunogenic drug (oxaliplatin), but not a non-immunogenic one (5-FU), synergizes with the bacteria to activate both the innate and adaptive immunity in the TME, resulting in complete tumor remission and a sustained anti-tumor immunological memory in mice. The combination of oxaliplatin and bacteria greatly enhances the co-stimulatory and antigen-presenting molecules on antigen-presenting cells, which in turn bridge the cytotoxic T cells for cancer-cell killing. Our findings indicate that rational combination of bacterial therapy and immunogenic chemotherapy can promote anticancer immunity against the immunosuppressive TME.

Original languageEnglish
Pages (from-to)416-428
Number of pages13
JournalEMBO Molecular Medicine
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 15 2024
Externally publishedYes

Keywords

  • Bacteria Cancer Therapy
  • Differential Stress Resistance
  • Immunotherapy
  • Oxaliplatin; TME Remodeling

ASJC Scopus subject areas

  • Molecular Medicine

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