Photothermal Immunotherapy in Cancer Treatment

Photothermal immunotherapy harnesses near-infrared (NIR) light-activated agents to generate localised hyperthermia within tumours, inducing cancer cell death and promoting the release of tumour-associated antigens. This in situ antigen release can be coupled with immune-stimulating strategies—such as checkpoint blockade, adjuvant delivery or metabolic enzyme inhibition—to amplify dendritic cell activation and cytotoxic T-cell responses. By converting a “cold” immunosuppressive microenvironment into a “hot” one, photothermal approaches can not only ablate primary lesions but also elicit systemic antitumour immunity against untreated or metastatic deposits. Advances in nanoparticle design enable co-delivery of photothermal agents and immunomodulators, precise control over thermal dose and real-time imaging guidance. Collectively, these innovations aim to enhance tumour eradication, prevent recurrence and establish long-lasting immune memory, offering a versatile platform for combination regimens across diverse cancer types.

Research from Nature Portfolio

Seminal work demonstrated that biodegradable polymer nanoparticles co-encapsulating a clinical photothermal dye and a Toll-like-receptor-7 agonist could ablate primary tumours under NIR irradiation, generate tumour-associated antigens and act as an adjuvant to prime immunity. When combined with CTLA-4 checkpoint blockade, this approach inhibited metastasis and established immunological memory in murine models, paving the way for multi-component photothermal vaccines. Building on this, polydopamine-coated spiky gold nanoparticles paired with a low dose of chemotherapy were shown to not only eliminate primary and distant tumours via a single treatment but also to stimulate robust antitumour T-cell responses. More recently, a lipid-gel depot containing a NIR photothermal probe and anti-PD-L1 antibody achieved controlled mild heating within tumours, enhancing lymphocyte infiltration in otherwise “cold” cancers and potentiating checkpoint blockade efficacy through on-demand antibody release.

Photothermal Immunotherapy in Cancer Treatment publication trend

The graph below shows the total number of articles in photothermal immunotherapy in cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Photothermal therapy (PTT): Use of agents that absorb NIR light and convert it into heat to ablate tumour cells and release antigens.

Immune checkpoint blockade: Inhibition of regulatory receptors (e.g., CTLA-4, PD-1/PD-L1) on T cells to enhance antitumour immunity.

Tumour microenvironment (TME): The cellular, molecular and structural milieu surrounding tumour cells, influencing therapeutic response.

Abscopal effect: Regression of untreated distant tumours following local therapy due to systemic immune activation.

Adjuvant: A compound that enhances antigen presentation and stimulates immune response against released tumour antigens.

References

1. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nature Communications (2016).
2. Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer. Nature Communications (2018).
3. Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy. Nature Communications (2019).
4. Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy. Advanced Science (2018).
5. NIR‐Triggered Phototherapy and Immunotherapy via an Antigen‐Capturing Nanoplatform for Metastatic Cancer Treatment. Advanced Science (2019).
6. Supramolecular Photothermal Nanomedicine Mediated Distant Tumor Inhibition via PD-1 and TIM-3 Blockage. Frontiers in Chemistry (2020).