Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer.
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.
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Houston, Texas, United States of America.
Adham S
AS
Bear
Laura C
LC
Kennedy
Joseph K
JK
Young
Serena K
SK
Perna
Joao Paulo
JP
Mattos Almeida
Adam Y
AY
Lin
Phillip C
PC
Eckels
Rebekah A
RA
Drezek
Aaron E
AE
Foster
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D006046:Gold / Q000627:therapeutic use*; D006979:Hyperthermia, Induced; D016219:Immunotherapy, Adoptive; D018836:Inflammation Mediators / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D022423:Myeloid Cells / Q000473:pathology; D057145:Nanoshells / Q000627:therapeutic use*; D010047:Ovalbumin; D010789:Phototherapy; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology*
D018925:Chemokines; D018836:Inflammation Mediators; D006046:Gold; D010047:Ovalbumin