Immune Response and Tumor Immunity following PDT
- Avdic Erma B.Sc., master student (Erma.AvdicATstud.sbg.ac.at)
- Verwanger Thomas Dr., assistant (Thomas.VerwangerATsbg.ac.at)
Expression of immune stimulating factors of CT26 mouse colon carcinoma cells under hypoxic conditions
Previous investigations showed complete regression of CT26 induced tumors in BALB/c mice after low-dose hypericin-PDT, very likely by vascular damage. In addition, mice showed an anti-tumor response against re-challenge with CT26 tumor cells. This response, likely based on a cytotoxic T-cell reaction, bears the potential to eliminate metastases or tumor cells surviving PDT, a shortcoming of the local PDT. It is therefore of major interest to investigate this potential in detail.
From these previous results it can be concluded that CT26 tumor cells were damaged and killed not directly by, but as a consequence of hypericin-PDT: by photo-destruction of the tumor-supporting vessels the tumor cells are cut from oxygen supply, by this inducing hypoxic conditions.
Hypoxia in turn is known to induce a wide range of cellular reactions, ranging from altered gene expression for e.g. adaptive or repair mechanisms up to lethal damage.
The message from damaged tumor cells to the immune system, which causes it to attack the same cell type arises inter alia 1) from tumor-associated macrophages (TAMs), which clear dead tumor cells by phagocytosis – mediated by pro-inflammatory cytokines in the case of necrosis. For the kind of reaction of the TAMs to dead tumor cells the cell death mode (apoptosis or necrosis) is decisive. 2) The message may be induced by immunogenic factors such as damage-associated molecular pattern (DAMPs) of the tumor cells, which have to be presented on the cell surface or released from the cells in order to induce an immune response.
Sanovic R, Verwanger T, Hartl A, Krammer B. Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma. Photodiagnosis Photodyn Ther. 2011 Dez; 8(4): 291-6.