Abstract

The use of attenuated bacteria as cancer therapeutic tools has garnered increasing scientific interest over the past 10 years. This is largely due to the development of bacterial strains that maintain good anti-tumor efficacy, but with reduced potential to cause toxicities to the host. Because of its ability to replicate in viable as well as necrotic tissue, cancer therapy using attenuated strains of facultative anaerobic bacteria, such as Salmonella, has several advantages over standard treatment modalities, including chemotherapy and radiotherapy. Despite some findings suggesting that it may operate through a direct cytotoxic effect against cancer cells, there is accumulating evidence demonstrating that bacterial therapy acts by modulating cells of the immune system to counter the growth of the tumor. Herein, we review the experimental evidence underlying the success of bacterial immunotherapy against cancer and highlight the cellular and molecular alterations in the peripheral immune system and within the tumor microenvironment that have been reported following different forms of bacterial therapy. Our improved understanding of these mechanisms should greatly aid in the translational application of bacterial therapy to cancer patients.

Highlights

  • Reviewed by: Michael Kogut, Agricultural Research Service (USDA), United States Caitlin S

  • The most common species of bacteria being used as immunotherapeutic agents are Clostridium novyi [3, 4], Listeria monocytogenes [5, 6], and Salmonella enterica serovar Typhimurium [6,7,8,9,10]

  • Monocytes are recruited to sites of tumor growth in response to chemoattractants released by tumor cells, such as colony stimulating factor 1 and the chemokine C-C motif chemokine ligand 2 (CCL2) [17], where they differentiate into macrophages

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Summary

Attenuated Bacteria as immunotherapeutic tools for cancer treatment

Later on he developed a safe vaccine, a mixture of heat killed S. pyrogenes and Seretia marcescenes, to successfully treat sarcoma, carcinoma, lymphoma, melanoma, and myeloma [2] These procedures practiced by Coley formed the basis of the recent advances in the cancer immunotherapy using attenuated bacterial strains. There is evidence that some bacterial components, such as exotoxins, may initiate anti-tumor activities by indirect activation of the immune system, and by their direct action on tumor cells [11, 12] In addition to their immunotherapeutic properties against diverse types of cancers, Salmonella and Listeria are used as vectors for delivering immunogenic tumor antigens to the host. We aim to review the direct effects of bacterial immunotherapeutic agents on different cellular components of the immune system

EFFECTS OF BACTERIAL THERAPY ON MYELOID CELLS
Dendritic Cells and TANs
NK Cells
EFFECT OF BACTERIAL THERAPY ON IMMUNOSUPPRESSIVE CELLS
Regulatory T Cells
CONCLUDING REMARKS
Findings
AUTHOR CONTRIBUTIONS
Full Text
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