T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?

Autor(es)

Anzengruber, Florian ^{[1, 2]} ; Avci, Pinar ^{[1, 2, 3]} ; de Freitasa, Lucas Freitas ^{[1, 2, 4]} ; Hamblin, Michael R. ^{[1, 2, 5]}

Afiliação do(s) autor(es)

^[1] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 - USA

^[2] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 - USA

^[3] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest - Hungary

^[4] Univ Sao Paulo, Programa Pos Grad Interunidades Bioengn, Sao Carlos - Brazil

^[5] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA - USA

• Tipo de documento: Artigo Científico
• Fonte: PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES; v. 14, n. 8, p. 1492-1509, 2015.
• Citações Web of Science: 18

Resumo

Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naive mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients. (AU)

• Processo FAPESP: 13/20599-4 - Síntese, caracterização e avaliação de citotoxicidade de complexos de nanobarras de ouro-ftalocianinas
• Beneficiário: Lucas Freitas de Freitas
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado