Insight into the Crosstalk between Photodynamic Therapy and Immunotherapy in Breast Cancer

Abstract

Breast cancer (BC) is the world’s second most frequent malignancy and the leading cause of mortality among women. All in situ or invasive breast cancer derives from terminal tubulobular units; when the tumor is present only in the ducts or lobules in situ, it is called ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS). The biggest risk factors are age, mutations in breast cancer genes 1 or 2 (BRCA1 or BRCA2), and dense breast tissue. Current treatments are associated with various side effects, recurrence, and poor quality of life. The critical role of the immune system in breast cancer progression/regression should always be considered. Several immunotherapy techniques for BC have been studied, including tumor-targeted antibodies (bispecific antibodies), adoptive T cell therapy, vaccinations, and immune checkpoint inhibition with anti-PD-1 antibodies. In the last decade, significant breakthroughs have been made in breast cancer immunotherapy. This advancement was principally prompted by cancer cells’ escape of immune regulation and the tumor’s subsequent resistance to traditional therapy. Photodynamic therapy (PDT) has shown potential as a cancer treatment. It is less intrusive, more focused, and less damaging to normal cells and tissues. It entails the employment of a photosensitizer (PS) and a specific wavelength of light to create reactive oxygen species. Recently, an increasing number of studies have shown that PDT combined with immunotherapy improves the effect of tumor drugs and reduces tumor immune escape, improving the prognosis of breast cancer patients. Therefore, we objectively evaluate strategies for their limitations and benefits, which are critical to improving outcomes for breast cancer patients. In the concluding section, we offer many avenues for further study on tailored immunotherapy, such as oxygen-enhanced PDT and nanoparticles.

Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer

“…Photodynamic therapy (PDT), which employs a photosensitizer to generate light-induced ROS, along with immunotherapy overcome the immune tolerance [ 311 ]. PDT-induced oxidative stress leads to calreticulin-mediated necrosis of tumor cells and secretes damage-associated molecular patterns (DAMPs) to cause antigen-presenting T cell activation [ 312 ].…”

“…PDT-induced phagocytosis in macrophages results in CD8 + T-cell activation [ 314 ]. PDT inhibits immunosuppressive TME along with its anti-tumor immune response [ 311 ]. It is used with immunomodulatory agents to prevent metastasis through improved CD8 + T cell stimulation [ 315 ].…”

Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines

“…Breast cancer, in addition to being the second most commonly diagnosed cancer type among women, also ranks as the second leading cause of cancer-related deaths in women under the age of 40. , Despite the current breast cancer treatment methods, which include surgery, radiotherapy, chemotherapy, and targeted therapy, the frequency and significance of the disease necessitate the need for new treatments. , Photodynamic therapy (PDT) has emerged as one of the most important methods used in the treatment of cancer without the need for surgical intervention. − Photodynamic therapy makes use of reactive oxygen species produced by the irradiation of photosensitizers (PSs). PSs, which take their place as light-absorbing species in PDT processes, are synthetic or natural chemicals.…”

PDT-Induced Activation Enhanced by Hormone Response to Treatment

“…In another study from 2023 by Jin et al, [ 72 ] a number of studies have shown that immunotherapy combined with PDT enhances the results of anti-tumor drugs and reduces tumor immune escape. PDT combined with immunotherapy does not induce resistance.…”

“…Meanwhile, blood vessel injury and tumor cells also attract macrophage infiltration, which regulates macrophage polarization and enhances macrophage phagocytosis of tumor cells. Natural killer cells (NK cells) and dendritic cells (DCs) activate adaptive immune cells, such as monocytes, cytotoxic T lymphocytes (CTLs), and B cells, to enhance the overall immune response by releasing cytokines [ 72 ].…”