Intratumoral Injection of Propionibacterium acnes Suppresses Malignant Melanoma by Enhancing Th1 Immune Responses

Abstract

Malignant melanoma (MM) is an aggressive cutaneous malignancy associated with poor prognosis; many putatively therapeutic agents have been administered, but with mostly unsuccessful results. Propionibacterium acnes (P. acnes) is an aerotolerant anaerobic gram-positive bacteria that causes acne and inflammation. After being engulfed and processed by phagocytes, P. acnes induces a strong Th1-type cytokine immune response by producing cytokines such as IL-12, IFN-γ and TNF-α. The characteristic Th2-mediated allergic response can be counteracted by Th1 cytokines induced by P. acnes injection. This inflammatory response induced by P. acnes has been suggested to have antitumor activity, but its effect on MM has not been fully evaluated.We analyzed the anti-tumor activity of P. acnes vaccination in a mouse model of MM. Intratumoral administration of P. acnes successfully protected the host against melanoma progression in vivo by inducing both cutaneous and systemic Th1 type cytokine expression, including TNF-α and IFN-γ, which are associated with subcutaneous granuloma formation. P. acnes-treated tumor lesions were infiltrated with TNF-α and IFN-γ positive T cells. In the spleen, TNF-α as well as IFN-γ producing CD8+T cells were increased, and interestingly, the number of monocytes was also increased following P. acnes administration. These observations suggest that P. acnes vaccination induces both systemic and local antitumor responses. In conclusion, this study shows that P. acnes vaccination may be a potent therapeutic alternative in MM.

Specific Humoral Immune Response Induced by Propionibacterium acnes Can Prevent Actinobacillus pleuropneumoniae Infection in Mice

“…Moreover, P. acnes is rarely identified as a cause of significant infection (11). In the present study, P. acnes induced biological effects that modulate the innate and acquired immune responses, causing increased phagocytic and tumoricidal activities in macrophages (12)(13)(14), increased antibody responses (15,16), and increased resistance to different pathogens (15,17). Therefore, the use of P. acnes and its components as immune enhancers and antineoplastic agents has become a focus in clinical and basic research.…”

Gut microbiome and anticancer immune response: really hot Sh*t!

“…Intratumoral inoculation of 3 mg of heat-killed Propionibacterium acnes in subcutaneous melanoma could promote local and systemic Th1 and Tc1 responses associated with in situ granuloma formation and tumor regression. 67 P. acnes is recognized by TLR2 on monocytes, macrophages and DCs, leading to the activation of IL-12 promotor. 68 Therefore, it is conceivable that certain commensals be involved in the natural immunosurveillance of malignancies exposed to the portals of entry (such as ulcerated melanoma).…”

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

“…Immunotherapy as intratumoral therapy has also been investigated: (a) Propionibacterium acnes induces immunestimulation by increasing interleukin-12, tumor necrosis factor-α, and interferon-γ,77 (b) secondary lymphoid chemokine and unmethylated cytosine-phosphorothioate-guanine-oligodeoxynucleotide were used to mobilize lymphocytes and dendritic cells and increased the infiltration of CD4 + T-cells and CD11c + cells in the tumor mass with observed reduction in tumor mass,78 (c) hu14.18-interleukin-2 administration resulted in increased natural killer (NK) group 2, member D receptors on intratumoral NKG2A/C/E + NKp46 + NK cells,79 (d) OK-432 efficiently suppressed metastatic squamous cell carcinoma lesion by inducing interferon-γ and tumor necrosis factor-α,80 (e) pre-treatment with cyclophosphamide and oligodeoxynucleotides plus rituximab enhanced immune activation against tumor cells and reduced tumor evolution,81 (f) dendritic cells and dendritic cells plus cyclophosphamide or paclitaxel at low doses enhanced immune system activation,82,83 (g) anti-gal antibody injection 84. Furthermore, several biomarkers were used specifically in intratumoral therapies as independent predictive factors, such as T cells and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an inhibitor of lovastatin, as a formulation that blocks local metastasis after irradiation 85…”