Induction of T cell responses and recruitment of an inflammatory dendritic cell subset following tumor immunotherapy with Mycobacterium smegmatis
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Mycobacteria and their cell wall components have been used with varying degrees of success to treat tumors, and Mycobacterium bovis BCG remains in use as a standard treatment for superficial bladder cancer. Mycobacterial immunotherapy is very effective in eliciting local immune responses against solid tumors when administered topically; however, its effectiveness in eliciting adaptive immune responses has been variable. Using a subcutaneous mouse thymoma model, we investigated whether immunotherapy with Mycobacterium smegmatis, a fast-growing mycobacterium of low pathogenicity, induces a systemic adaptive immune response. We found that M. smegmatis delivered adjacent to the tumor site elicited a systemic anti-tumor immune response that was primarily mediated by CD8+ T cells. Of note, we identified a CD11c+CD40intCD11bhiGr-1+ inflammatory DC population in the tumor-draining lymph nodes that was found only in mice treated with M. smegmatis. Our data suggest that, rather than rescuing the function of the DC already present in the tumor and/or tumor-draining lymph node, M. smegmatis treatment may promote anti-tumor immune responses by inducing the involvement of a new population of inflammatory cells with intact function.
KeywordsMycobacterium smegmatis Immunotherapy Dendritic cell Thymoma Mycobacteria BCG
This work was supported by research grants from the Cancer Society of New Zealand and from the Malaghan Institute of Medical Research. Joanna Kirman is the Wellington Medical Research Foundation Malaghan Haematology Fellow; Sabine Kuhn was supported by a PhD scholarship from DAAD and Victoria University of Wellington. The authors thank the Biomedical Research Unit at the Malaghan Institute for their excellent animal husbandry, and Kelly Prendergast and Lindsay Ancelet for assistance with experiments.
Conflict of interest
The authors declare that they have no conflicts of interest.
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