Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer

• Published in: PloS one Vol. 8; no. 7; p. e69073
• Main Authors: Bear, Adham S, Kennedy, Laura C, Young, Joseph K, Perna, Serena K, Mattos Almeida, Joao Paulo, Lin, Adam Y, Eckels, Phillip C, Drezek, Rebekah A, Foster, Aaron E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.07.2013; Public Library of Science (PLoS)
• Subjects: Ablation; Ablation (Surgery); Animals; Antitumor activity; Bioengineering; Biology; Cancer metastasis; Cancer therapies; Cancer treatment; CD11b antigen; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Chemokines; Chemokines - metabolism; Children & youth; Computer engineering; Cytokines; Dendritic cells; Dendritic Cells - metabolism; Gene therapy; Glycoprotein gp100; Gold; Gold - therapeutic use; Hyperthermia, Induced; Immune response; Immune system; Immunity; Immunogenicity; Immunology; Immunomodulation; Immunotherapy; Immunotherapy, Adoptive; Infiltration; Inflammation; Inflammation Mediators - metabolism; Laboratory animals; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lungs; Ly-6 antigen; Lymph nodes; Lymph Nodes - pathology; Lymphocytes; Lymphocytes T; Medical research; Medicine; Melanoma; Melanoma - immunology; Melanoma - therapy; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Metastases; Metastasis; Mice; Myeloid Cells - pathology; Nanoshells - therapeutic use; Oncology; Oryza; Ovalbumin; Phototherapy; Priming; Recurrence; Suppressor cells; T cells; T-Lymphocytes - immunology; Therapy; Tumors; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069073

Ablative treatments such as photothermal therapy (PTT) are attractive anticancer strategies because they debulk accessible tumor sites while simultaneously priming antitumor immune responses. However, the immune response following thermal ablation is often insufficient to treat metastatic disease. Here we demonstrate that PTT induces the expression of proinflammatory cytokines and chemokines and promotes the maturation of dendritic cells within tumor-draining lymph nodes, thereby priming antitumor T cell responses. Unexpectedly, however, these immunomodulatory effects were not beneficial to overall antitumor immunity. We found that PTT promoted the infiltration of secondary tumor sites by CD11b(+)Ly-6G/C(+) myeloid-derived suppressor cells, consequently failing to slow the growth of poorly immunogenic B16-F10 tumors and enhancing the growth of distant lung metastases. To exploit the beneficial effects of PTT activity against local tumors and on antitumor immunity whilst avoiding the adverse consequences, we adoptively transferred gp100-specific pmel T cells following PTT. The combination of local control by PTT and systemic antitumor immune reactivity provided by adoptively transferred T cells prevented primary tumor recurrence post-ablation, inhibited tumor growth at distant sites, and abrogated the outgrowth of lung metastases. Hence, the combination of PTT and systemic immunotherapy prevented the adverse effects of PTT on metastatic tumor growth and optimized overall tumor control.