Photodynamic Therapy and Antitumor Immunity

Photodynamic therapy (PDT) constitutes a minimally invasive modality for cancer treatment that relies on photoactivation of a light‐sensitive agent, yielding reactive oxygen species (ROS) that inflict localised tumour cell destruction and vascular damage. Beyond direct cytotoxicity, PDT triggers immunogenic cell death (ICD), characterised by surface exposure and release of damage‐associated molecular patterns (DAMPs) such as calreticulin, heat shock proteins and high mobility group box 1. These molecular cues promote recruitment and maturation of dendritic cells and other antigen‐presenting cells, thereby bridging innate and adaptive immunity. Consequently, PDT can elicit tumour‐specific cytotoxic T lymphocyte responses and establish immunological memory, offering the potential to control both primary lesions and micrometastases. The interplay between the tumour microenvironment, photosensitiser pharmacokinetics and light‐delivery parameters has been shown to influence the magnitude and quality of the antitumour immune response. Recent advances have focused on combining PDT with immunotherapeutic agents—such as immune checkpoint inhibitors and ferroptosis modulators—to amplify systemic immunity and overcome immune‐suppressive barriers. Ongoing research aims to refine photosensitiser formulations, optimise light dosimetry and integrate PDT within multimodal protocols to maximise efficacy across diverse cancer types and stages.

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Photodynamic Therapy and Antitumor Immunity publication trend

The graph below shows the total number of articles in photodynamic therapy and antitumor immunity across all publications each year (not limited to Nature Index journals).

Technical terms

Photodynamic therapy (PDT): A treatment modality using a photosensitising agent activated by specific light wavelengths in the presence of oxygen to produce reactive oxygen species and destroy target cells.

Photosensitiser: A light‐sensitive compound that accumulates preferentially in tumour tissues and generates cytotoxic species upon illumination.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that cause oxidative damage to cellular components, leading to cell death.

Immunogenic cell death (ICD): A form of regulated cell death that elicits an adaptive immune response through exposure and release of DAMPs.

Damage‐associated molecular patterns (DAMPs): Endogenous molecules exposed or released by stressed and dying cells that activate innate immune receptors and promote antigen presentation.

Adaptive immunity: The arm of the immune system characterised by antigen‐specific responses mediated by lymphocytes, leading to immunological memory.

References

1. Enhanced Photodynamic Therapy Synergizing with Inhibition of Tumor Neutrophil Ferroptosis Boosts Anti‐PD‐1 Therapy of Gastric Cancer. Advanced Science (2024).
2. The impact of photodynamic therapy on immune system in cancer – an update. Frontiers in Immunology (2024).
3. Immunogenic Cell Death: Can It Be Exploited in PhotoDynamic Therapy for Cancer?. BioMed Research International (2012).
4. Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response. PLOS ONE (2010).
5. Current Challenges and Opportunities of Photodynamic Therapy against Cancer. Pharmaceutics (2023).