• The future of cancer treatment: advancing immuno-radiotherapy with innovative techniques
  • Elahe Roohbakhsh amoli moghadam,1 Erfan Shapourgan,2 Ali Asghar Fallah,3 Hassan Borji,4,*
    1. Department of Clinical Science,faculty of Vetrinary Medicine,Ferdowsi Universuty of Mashhad
    2. Department of medicine,Tehran University of Medical Science
    3. Department of Biology,Faculty of basic sciences,Islamic Azad University, Mashhad Branch,Iran
    4. Department of Pathobiology of Vetrinary Medicine,Ferdowsi University of Mashhad


  • Introduction: For the majority of cancer types, radiotherapy has been used to treat them since the early 1950s, and it is one of the most widely used treatments today. The induction of tumor cell death by ionizing radiation has the effect of either eliciting Immunosuppression or immune responses that protect against tumors, which contributes to the recurrence of local tumors after radiation treatment. There is a growing body of evidence that immunosuppression has the potential to lead to the Activation of immune suppressor cells, such as neutrophils, tumor-associated macrophages (TAMs), T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSCs), as well as the release of immunosuppressive cytokines (TGF- β, IL-10) and chemokines. As a combination with RT, it has been shown that many primary and metastatic cancers can be treated with immunotherapies based on checkpoint blockade. . These immunotherapies include anti-PD-1 and anti-PD-L1 antibodies. It is also known that RT can be enhanced by using vaccines, cytokines, immunoglobulins, and adaptive immune cells transferred from one patient to another (NK cells, T cells, DCs). In the present review, we will summarize the currently available data on the immunological rationale behind the combination of RT with various immunotherapies.
  • Methods: In order to retrieve published data (from 2000 to 2023), databases including Scopus, PubMed, ScienceDirect, and Google Scholar were used. This search strategy involved downloading and retrieving published literature. There were specific keywords used in the search, such as " radiotherapy ", ”immunotherapy”, ”immune suppressor cells”, ” immunosuppressive cytokines”, ” immunosuppressive chemokines”. In total, 500 studies have been conducted. A total of 400 abstracts were excluded, and 100 full-text studies were read. An analysis of 30 relevant articles with complete abstracts was conducted in the final inclusion criteria.
  • Results: One of the novel approaches for improving the effectiveness of immuno-radiotherapy is the integration of cutting-edge immunotherapies with radiation therapy to enhance the immune system's response to cancer and enhance the immune system's ability to fight cancer. A customized treatment plan is developed for each patient based on their immune profile and tumor characteristics, and immune checkpoint inhibitors and adoptive cell therapies are combined with radiation therapy for treatment. Researching the development of innovative immunomodulatory substances like STING agonists and oncolytic viruses for reducing immune suppression. In addition, we are fine-tuning radiation doses to reduce immune suppression and experimenting with specialized immunomodulatory substances, such as nanoparticles, for precise radiation delivery and immune regulation. As a result of the synergy between radiation and immunotherapy, cancer patients with these innovative approaches will have better long-term survival outcomes and better control of their tumors. Researchers have shown that patients with advanced non-small cell lung cancer have a significant improvement in local control of metastatic tumors and improved overall survival when they combine immune checkpoint inhibitors (such as pembrolizumab or nivolumab) with stereotactic body radiation therapy (SBRT). The researchers have successfully engineered nanoparticles coated with immune-stimulating agents, such as toll-like receptor agonists, and these nanoparticles are demonstrated to have remarkable tumor-targeting capabilities when combined with radiation therapy in preclinical models. It has been shown that oncolytic viruses can be used together with radiotherapy to promote tumor-specific immune activation in a way that has proven to be very effective. A cancer cell is selectively infected and destroyed, and immune cells are recruited to mount a powerful antitumor response, increasing the chances of a successful therapeutic response.
  • Conclusion: In view of these developments, immuno-radiotherapy holds great promise as a cancer treatment and could be used in the future. A number of new approaches are currently being explored and developed to enhance its efficacy in order to make it more effective. As research and clinical teams strive to maximize the therapeutic potential of radiation therapy and immunotherapy, a combination of personalized treatment plans, immunomodulatory agents, and innovative delivery systems is being explored. The purpose of these efforts is not only to expand our understanding of the complex interactions between radiation and the immune system but also to improve patient outcomes, minimize treatment-related toxicity, and push the boundaries of cancer treatment in the process. Continually developing these novel strategies holds substantial promise for the future development of cancer therapies and the possibility of providing renewed hope to those who suffer from the disease.
  • Keywords: radiotherapy,immunotherapy,immune suppressor cells,immunosuppressive cytokines