مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Combination of cancer immunotherapies involving CD47/SIRPα inhibition for the treatment of melanoma: a systematic review of animal studies
Combination of cancer immunotherapies involving CD47/SIRPα inhibition for the treatment of melanoma: a systematic review of animal studies
Mohammad-Salar Hosseini,1,*Farhad Jadidi-Niaragh,2Sarvin Sanaie,3Ata Mahmoodpoor,4
1. Hematology and Oncology Research Center, Tabriz University of Medical Sciences 2. Department of Immunology, Immunology Research Center, Tabriz University of Medical Sciences 3. Aging Research Institute, Tabriz University of Medical Sciences 4. Department of Anesthesiology and Intensive Care, Faculty of Medicine, Tabriz University of Medical Sciences
Introduction: Originating in melanocytes, melanoma remains a formidable challenge in clinical oncology, demanding innovative therapeutic approaches to enhance treatment outcomes. Over the past decade, emerging research has spotlighted the potential of targeting CD47 as a promising strategy in cancer therapy. CD47, a cell surface protein, plays a pivotal role in immune evasion and self-tolerance maintenance by transmitting anti-phagocytic signals. Recent studies suggest that the overexpression of CD47 on cancer cells can serve as a "do not eat me" signal to evade phagocytic clearance. SIRPα, a receptor expressed on the surface of macrophages, also plays a crucial role in mediating the same signal in cancer cells through its interaction with CD47. Inhibition of the CD47/SIRPα axis has shown promising effects in melanoma research by promoting macrophage-mediated phagocytosis of tumor cells, potentially enhancing anti-tumor immune responses and affecting the tumor immune escape and therapeutic resistance. Recent studies have proposed a synergistic potential for combining CD47/SIRPα-targeting therapies with other immunotherapy strategies. We aim to review the evolving landscape of CD47/SIRPα targeting combination therapies for the treatment of melanoma.
Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed to conduct this study. A systematic literature search was conducted in Medline (via PubMed), Scopus, Web of Science, and the Cochrane Library databases with no limit in time and language until August 2023. The search strategy was developed using a proper combination of MeSH terms and free keywords representing CD47, SIRPα, melanoma, and their equivalents. The results were screened for relevance by title/abstract and full-text article, and all animal studies with at least one arm of CD47/SIRPα-targeting intervention combined with other immunotherapy treatments, were included. Studies of CD47/SIRPα-targeting monotherapies were excluded. Conference proceedings, clinical studies, and reviews were also excluded. The included records were critically appraised for methodological quality by two independent contributors, using the JBI critical appraisal tools, and the points of disagreement were referred to a third contributor. Two independent contributors extracted all relevant data using a standardized data extraction tool.
Results: From a total of 505 search results, six studies meeting the inclusion and exclusion criteria were included in this review. Five studies were conducted by implanting B16-F10 cells in C57BL/6 mice, while one used A375 melanoma NOG mice. Immune checkpoint inhibitors were part of the combined approach in all included studies, with the PD-1/PD-L1 axis as the adjuvant target in four and CTLA-4 in two studies. A4 (anti-mouse CD47 nanobody) was the most common CD47/SIRPα-targeting agent. Inhibited tumor growth was observed among all studies, and three studies reported improved survival. PD-1/PD-L1 combination also showed a durable and lasting immune memory response. Meanwhile, one study combining A4 with αCTLA-4 antibodies and an autologous GM-CSF–secreting tumor vaccine (GVAX) resulted in considerable toxicity.
Conclusion: Our systematic review of animal studies investigating the combination of cancer immunotherapies involving CD47/SIRPα inhibition for the treatment of melanoma underscores the synergistic potential of this approach. The combination of CD47/SIRPα-targeting agents and other immunotherapy strategies seems to provide an effective and comprehensive treatment for melanoma; however, more studies combining CD47/SIRPα axis inhibition with other immunotherapies and conventional cancer treatments, such as chemotherapy and radiotherapy, are required. Undoubtedly, the ultimate decision about the effectiveness and safety of this approach depends on the results of future clinical studies.