Advances in photothermal-driven tumor immunomodulation and synergistic therapy

Photothermal therapy (PTT) is a local treatment that uses photothermal conversion agents (PTAs) to absorb light and produce heat in tumor tissue. The direct result is tumor ablation. At the same time, heat-damaged tumor cells may undergo immunogenic cell death (ICD). This process is often accompanied by the release of damage-associated molecular patterns (DAMPs), followed by dendritic cell activation and antigen presentation. Because of this immune effect, PTT has been explored as a partner for immunotherapy. It may be useful in tumors where antigen presentation is weak or where the immune microenvironment is highly suppressive. However, local heating alone usually cannot produce a long-lasting systemic immune response. Its effect on distant metastasis is also limited. For this reason, PTT is now often combined with immune checkpoint blockade, adoptive cell therapy, cancer vaccines, and other immune-based strategies. This review discusses the link between PTT-induced tumor damage and antitumor immune activation. It classifies and compares the structural optimization ideas, optical properties, biological safety, and application limitations of organic and inorganic photothermal materials. It summarizes the six mainstream combination schemes of photothermal therapy with immune checkpoint inhibitors, adoptive cell therapy, tumor vaccines, cytokine therapy, oncolytic virus therapy, and bispecific antibody therapy. It analyzes the synergistic anti-tumor mechanisms and the latest preclinical research progress of various combination strategies. Finally, it sorts out the core bottlenecks that restrict the clinical transformation of photothermal immunotherapy and proposes corresponding optimization development prospects.