Photodynamic therapy and anti‐tumor immunity

Abstract

Preclinical studies have shown that local photodynamic therapy (PDT) enhances systemic antitumor immunity. In addition, it has long been known that the long-term efficacy of PDT depends on the presence of an intact adaptive immune system. Years of research in the laboratory have attempted to shed light on the mechanisms of the PDT-enhanced antitumor immune response, suggesting that increased expression of proinflammatory cytokines may play a key role. This overview on the immunologic potential of PDT briefly explores these proposed mechanisms and addresses preliminary results with PDT vaccines in combination with surgery as perhaps a new clinical strategy for cancer treatment outside the laboratory. PDT and Antitumor Immunity: Moving From Mice to Humans"Long-term PDT efficacy depends upon the presence of an intact adaptive immune system," declared Dr. Gollnick. Preclinical studies using mice models and clinical studies in patients have shown that PDT is capable of influencing the immune system. 2 Studies have also shown that response to PDT is limited in immunosuppressed patients, she added. "When we do PDT in immunocompetent BALB/c mice, we get a very good response, but when we do it in immunosuppressed or immunoincompetent mice, we don't get the response," reported Dr. Gollnick. However, the response is restored when CD8+ T cells are given back to the mice, suggesting that PDT-enhanced antitumor immunity may be mediated by CD8+ T cells. of neutrophilic infiltrate-generated tumor-specific T-cell responses, whereas a PDT regimen that induces little or no neutrophilic infiltrate exhibited minimal antitumor activity. 1 "We showed this in animals for a decade and then did it on patients," revealed Dr. Gollnick. The first actual study in humans tested the immune response to PDT in patients with basal cell carcinoma. 3 "Our laboratory defined an antigen that is overexpressed on basal cell carcinomas Hip1 (a member of the sonic hedgehog pathway)," she explained. The lesions were either treated with PDT or surgically removed. Both before and after PDT, "we saw an increased T-cell response against that Hip1 antigen that we did not see following surgery," Dr. Gollnick reported. This systemic antitumor immune response was inversely correlated with treatment area and dose.

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

“…Thus it is possible that local PDT treatment of tumours leads to release of factors capable of bypassing the need for CD4 þ T cells in the activation of DCs. In support of this hypothesis, we have recently shown that PDT treatment of EMT6 and Colon26 tumours enhances maturation and activation of DCs and that DCs isolated from PDT treated mice are able to stimulate T-cell effector functions (Gollnick et al, 2006).…”

Therapeutic and immune effects of 5‐aminolevulinic acid photodynamic therapy on UVB‐induced squamous cell carcinomas in hairless mice

“…PDT generated inflammatory mediators together with components released from tumor cells can also activate antigen presenting cells capable of stimulating effector T-cell proliferation and cytokine secretion (11). Recently, Yokogawa et al (12) demonstrated that topical Imiquimod, a Toll-like receptor 7/8 agonist, could trigger T-cell infiltrates in SCCs.…”

Photodynamic therapy-generated vaccines: relevance of tumour cell death expression

“…The destruction of targeted lesions by PDT results from localised production of reactive oxygen species mediated by drugs (photosensitisers) capable of capturing the energy of light and transferring it to molecular oxygen (Henderson and Dougherty, 1992;Dougherty et al, 1998). Unlike immunologically silent genotoxic damage produced by radiotherapy and chemotherapy, photooxidative cytotoxic lesions generated by PDT are extranuclear and result in a rapid cell death that alerts host's immune surveillance elements (Castano et al, 2006;Gollnick et al, 2006;Korbelik, 2006). Hence, tumour PDT induces a strong host response mediated by innate immune system and characterised by overt inflammatory and acute phase responses that culminates in the acquirement of adaptive immunity recognising the treated tumour as its target (Korbelik, 2006).…”