In-depth understanding of the mechanisms of combined Photodynamic and CpG oligodeoxynucleotide-based Immunotherapy for cervical cancer treatment

• Grant number: 25/24184-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: January 26, 2026
• End date: March 13, 2026
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Principal Investigator: Natalia Mayumi Inada
• Grantee: Flávia Langellotti Silva
• Supervisor: Vladislav Yakovlev
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: Texas A&M University, United States
• Associated to the scholarship: 24/08873-8 - Development of a protocol and understanding of the mechanisms of action of the combination of Photodynamic Therapy and Immunotherapy using oligodeoxynucleotides with CpG sequences in the treatment of cervical cancer, BP.IC

Abstract

Cervical cancer (CC) ranks fourth globally among the most common and deadly types of malignant neoplasms for women. Although several treatments are available, such as hysterectomy, radiation therapy, and chemotherapy, the negative impacts on the patient's life after treatment are alarming, including loss of fertility, sexual dysfunction, and premature ovarian failure. In this context, Photodynamic Therapy (PDT) emerges as a possible solution, as it is a non-invasive treatment approved for clinical use. Through a reaction between a photosensitizer, oxygen, and light, the generation of reactive oxygen species (ROS) is responsible for cancer cell death. With this non-invasive approach, it is possible to preserve reproductive potential, manage outpatient management, and minimize the side effects of treatment for patients with cervical cancer. It is understood that lymphocytes in an inflamed or cancerous microenvironment are stimulated to produce IFN-¿ by locally present interleukins, such as IL-12, an interleukin produced by dendritic cells immunostimulated by local cytokines or by immunomodulatory agents, such as Class A CpG oligodeoxynucleotides (ODN - CpG Class A ), used in experiments conducted in Brazil. Furthermore, in vitro studies demonstrate that IFN-¿ can increase the cellular expression of the major histocompatibility producing complex class I (MHC I). In this scenario, the Research Internship Abroad (BEPE) project aims to, using cervical cancer cells, understand the consequences of PDT and IL-12 on the mitochondrial respiration of cervical cancer cells, as well as the colocalization of the photosensitizer applied in the experiments performed in Brazil. Furthermore, the study seeks to define the impact of IFN-¿, an important cytokine in the tumor microenvironment, on HeLa cells treated with PDT. Therefore, these data obtained at Texas A&M University are expected to provide new, consistent knowledge that will enable the therapeutic combination under study to serve as the foundation for a change in current cervical cancer treatments, increasing the likelihood of cure and improving the patient's quality of life during treatment.