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WIREs Nanomed Nanobiotechnol
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The synergistic strategies for the immuno‐oncotherapy with photothermal nanoagents

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Abstract Immuno‐oncotherapy has shown great promise for the cure of late‐stage and metastatic cancer. Great efforts have tried to improve the overall response rate (ORR) and to reduce the immune‐related adverse events (irAEs). Antigen presentation, T cell activation and killing are interlocking and distinct steps to initiate effective anti‐tumor immune responses. Aiming to overcome the tumor immune evasion whose mechanisms include limited release of neoantigen, suppressed infiltration of antigen‐presenting cells (APCs) and T cells, and the expression of immune checkpoints (ICPs), combinational therapeutic strategies have shown great potential by activating the anti‐tumor immune responses together with deactivating immunosuppressive conditions simultaneously. In this direction, photothermal therapy (PTT) has attracted attention due to the efficient ablation of tumor cells, of which the released immunogenic tumor debris can activate host immune responses. The combination of immunoadjuvants and/or ICP inhibitors can boost the anti‐tumor immune responses, realizing PTT‐synergized immuno‐oncotherapy. In this regard, numerous multifunctional nanomaterials have been designed with integration of photothermal and immuno‐oncotherapeutic agents into one package via well‐designed surface modification and functionalization. This review summarizes the recent studies on the synergistic strategies for the immuno‐oncotherapy based on photothermal nanoagents and the mechanisms that trigger the systemic anti‐tumor immune responses and PTT‐synergized immuno‐oncotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
The immune responses against cancer. The anti‐tumor immune responses consist of five major steps including neoantigen release, antigen presentation, T cell activation, and T cell infiltration and killing. The tumor‐mediated immune suppressive factors and relative therapeutic strategies are indicated in red and green, respectively. DC, dendritic cell; ICP, immune checkpoint; CTLA‐4, cytotoxic T lymphocyte associated antigen 4; PD‐1, programmed death 1; PD‐L1, programmed death ligand 1; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor
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A schematic overview of the synergistic strategies for the immuno‐oncotherapy based on photothermal nanoagents. Under NIR laser irradiation, the photothermal agents (indocyanine green, gold nanomaterials, 2D nanomaterials, etc.) can ablate tumor cells, which causes the release of tumor‐associated antigens. Immunoadjuvants can be used to stimulate the DCs for their maturation. The matured DCs can capture and present these neoantigens to naive T cells for their activation and differentiation. Activated effector T cells can infiltrate into tumor sites and perform the anti‐tumor immune response, which can be enhanced by ICP blocking. The application of PTT can also break the stroma barrier of solid tumor, benefiting the T cells tumor infiltration
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