Inhibition of photodynamic therapy induced‑immunosuppression with aminolevulinic acid leads to enhanced outcomes of tumors and pre‑cancerous lesions (Review)

Abstract

Photodynamic therapy (PDT) is a treatment option for tumors and pre-cancerous lesions, but it has immunosuppressive side effects that limit its effectiveness. Recent studies suggest that PDT-mediated immunosuppression occurs through a cyclooxygenase type 2 (COX-2) mediated pathway that leads to increases in regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), which act as negative regulators of immune responses. Given this pathway, there are three main methods to block immunosuppression: i) Inhibiting the proliferation of Tregs, which can be achieved with the administration of cyclophosphamide or inhibitors of indoleamine 2,3-dioxygenase 1, an activator of Tregs; ii) inhibiting MDSCs by reducing hypoxia around the tumor to create an unfavorable environment or administering all-trans-retinoic acid, which converts MDSCs to a non-immunosuppressive state; and iii) inhibiting COX-2 through selective or non-selective COX-inhibitors. In the present review article, strategies that have shown increased efficacy of PDT in treating tumors and pre-cancerous lesions by blocking the immunosuppressive side effects are outlined and discussed.

Photodynamic therapy in the treatment of condyloma acuminata: A systematic review of clinical trials

“…36 A recent review also summarized 13 studies, showing PDT-induced immunosuppression effects, possibly involving cyclooxygenase-2 (COX-2), regulatory T cell (Tregs), and myeloid-derived suppressor cell (MDSCs) upregulation. 37…”

“…Hence, it can diminish the immunosuppression resulted by PDT. Lastly, simply decreasing the rate of irradiation may be another option in reducing immunosuppressive effects by PDT, 37 as it was previously reported that reduction in oxygen consumption through the administration of lower levels of irradiation (e.g. 15 mWÁcm À2 , 45 mWÁcm À2 , and 50 mWÁcm À2 ) can reduce the immunosuppressive effects of PDT.…”