Photodynamic therapy, or PDT, entails the use of a light-sensitizing agent that captures and transmit light energy to cause the destruction of diseased cells. One of the fascinating effects of PDT is that it can bolster the immune system’s ability to eliminate cancer.
This takes place in the following way. An infrared laser is focused on the tumor area using an approach known as laserthermia. This results in greatly increased temperature in the tumor tissue—in essence “cooking” and directly killing the tumor. As the tumor cells swell up and die, they release key proteins, the so-called tumor-associated antigens, or TAAs. These proteins, in turn, can stimulate the entire body’s immunity against cancer.
In the innovative approach increasingly referred to as immuno-PDT, photosensitizers again play a central role. The difference is the use of additional strategies for supporting the immune system. For example, adding interferon and other immune-modulating substances (generally referred to as immune adjuvants) can further improve the outcome of PDT.
A recent example of this is the use of a drug that inhibits a DNA enzyme inside the tumor, thus limiting the tumor’s ability to suppress the production of TAAs mentioned above. Tumors use this strategy to help fool the immune system into tolerating the cancer rather than mobilizing against the disease.
Immunologists at Center for Biostructure Research, based at the Medical University of Warsaw (Poland), recently reported that 5-aza-dC can restore the tumor’s production of TAAs. Those antigens essentially act as warning signals that help further marshal the immune defenses against the cancer. The resulting effects on immunity reinforce PDT’s ability to “eilicit robust and durable antitumor immunity,” as reported in the 15 May 2014 issue of Oncoimmunology.
In a subsequent report that was an extension of the above study, the same Warsaw research team then teamed up with the Polish Academy of Sciences as well as the Wellman Center for Photomedicine at Harvard Medical School (USA). The researchers confirmed that antitumor immune response can be further improved when PDT is combined with a clinically approved drug that induces the tumor’s expression of TAAs.
Implications of Cancer-Bolstering Immunity
The cancer-repelling immune effects of this strategy were demonstrated in experimental models of lung cancer, colon cancer and breast cancer. In these laboratory studies, the approach described above resulted in long-term survival, and all long-term surviving mice were resistant to re-inoculation with the same tumor cells.
Taken together, the findings suggest that strategies aimed at boosting TAAs could prove to be a novel way to further bolster the tumor-destroying impact of PDT by complementing the treatment’s favorable effects on anti-tumor immunity. These findings offer a rationale for clinical development of this or similar immuno-PDT strategies, as reported in the May 2014 European Journal of Cancer.
Another strategy, as reported in the August 2014 issue of Anticancer Research, involves the use of antibodies to the TAAs, and combining this with PDT. Such elegant applications of PDT may lead to therapeutic outcomes that far surpass what can be accomplished with the simpler forms of PDT, and they could soon prove superior to many conventional cancer treatment strategies as well.
Certainly the biological rationale behind the immuno-PDT strategy is an important direction for future research. Cancer immunity is a missing piece in many treatment strategies today. This perspective that should illuminate a whole new way of thinking about what constitutes truly effective cancer treatment.
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Wachowska M, Gabrysiak M, Muchowicz A, Bednarek W, Barankiewicz J, Rygiel T, Boon L, Mroz P, Hamblin MR, Golab J. 5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. Eur J Cancer. 2014 May;50(7):1370-81.
Wachowska M, Gabrysiak M, Golab J. Epigenetic remodeling combined with photodynamic therapy elicits anticancer immune responses. Oncoimmunology. 2014 May 15;3:e28837. eCollection 2014.
Kushibiki T, Hirasawa T, Okawa S, Ishihara M. Responses of cancer cells induced by photodynamic therapy. J Healthc Eng. 2013;4(1):87-108.
Kuroki M, Shirasu N. Novel treatment strategies for cancer and their tumor-targeting approaches using antibodies against tumor-associated antigens. Anticancer Res. 2014 Aug;34(8):4481-8.
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