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Molecules ; 26(12)2021 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205347

RESUMO

PURPOSE: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. EXPERIMENTAL DESIGN: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. RESULTS: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. CONCLUSIONS: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.


Assuntos
Receptor de Morte Celular Programada 1/agonistas , Receptores OX40/agonistas , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunidade/efeitos dos fármacos , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fotoquimioterapia/métodos , Linfócitos T/efeitos dos fármacos , Neoplasias Urológicas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
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