Intratumoral injection of Propionibacterium acnes suppresses malignant melanoma by enhancing Th1 immune responses.
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.
Department of Dermatology, Graduate School of Medicine, Mie University, Tsu, Mie, Japan.
Kenshiro
K
Tsuda
Keiichi
K
Yamanaka
Wang
W
Linan
Yoshihiro
Y
Miyahara
Tomoko
T
Akeda
Takehisa
T
Nakanishi
Hiroshi
H
Kitagawa
Masato
M
Kakeda
Ichiro
I
Kurokawa
Hiroshi
H
Shiku
Esteban C
EC
Gabazza
Hitoshi
H
Mizutani
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D015552:Injections, Intralesional; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D011425:Propionibacterium acnes / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger