Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy

Hyein Jeong; So-Young Lee; Hyejun Seo; Dong Hyun Kim; Duhyung Lee; Bum-Joon Kim

doi:10.1080/2162402X.2021.2023340

Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy

Oncoimmunology. 2022 Jan 20;11(1):2023340. doi: 10.1080/2162402X.2021.2023340. eCollection 2022.

Authors

Hyein Jeong^{1

2

3

4

5

6}, So-Young Lee^{1

3

4

5

6}, Hyejun Seo^{1

3

4

5

6}, Dong Hyun Kim^{1

2

3

4

5

6}, Duhyung Lee^{1

3

4

5}, Bum-Joon Kim^{1

2

3

4

5

6}

Affiliations

¹ Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, South Korea.
² Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, South Korea.
³ Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea.
⁴ Cancer Research Institute, College of Medicine, Seoul National University, Seoul, South Korea.
⁵ Institute of Endemic Diseases, Seoul National University Medical Research Center (SNUMRC), Seoul, South Korea.
⁶ BK21 Four Biomedical Science Project, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

For clinical application by dendritic cell (DC)-based cancer immunotherapy, a proper adjuvant system to elicit a strong anticancer immune response is needed. Here, we investigated the potential of chorismate mutase (TBCM, Rv1885c), a putative Mycobacterium tuberculosis (TB) virulence factor, as an immunoadjuvant in DC-based tumor immunotherapy. First, we found that TBCM functionally activated DCs by upregulating costimulatory molecules, increasing the secretion of proinflammatory cytokines, enhancing migration and inducing the Th1-type immune response in a dose-dependent manner via TLR4-mediated signaling. In addition, subcutaneous injection of TBCM-activated DCs loaded with cell lysates led to reduced tumor mass, enhanced mouse survival and lowered tumor incidence in lung carcinoma (LLC) cell-bearing mice. This is mainly mediated by functional cytotoxic T lymphocyte-mediated oncolytic activity and inhibition of cancer proliferation- and metastasis-related genes. Moreover, TBCM-induced DCs can also generate memory CD4 T cells and exert long-term tumor prevention effects. In conclusion, our findings suggest that TBCM (Rv1885c), a novel TLR4 agonist, could be used as an immunoadjuvant for DC-based cancer immunotherapy.

Keywords: Mycobacterium tuberculosis; TLR4 agonist; adjuvant; cancer immunotherapy; chorismate mutase (TBCM); dendritic cells.

MeSH terms

Adjuvants, Immunologic
Animals
Chorismate Mutase
Dendritic Cells
Immunotherapy
Mice
Mycobacterium tuberculosis*
Neoplasms* / therapy
Toll-Like Receptor 4 / genetics

Substances

Adjuvants, Immunologic
Tlr4 protein, mouse
Toll-Like Receptor 4
Chorismate Mutase

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.