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Interactions Between Platelets and Leukocytes in Ovarian Cancer: A New Approach to Cancer Treatment: A Review Publisher



Moradpanah S1 ; Mahabadi AAK2 ; Khodakarim N3 ; Maftoohi M4 ; Shirkosh P5 ; Amirlatifi S6 ; Dastyar F7
Authors
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Authors Affiliations
  1. 1. Department of Obstetrics and Gynecology, School of Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Obstetrics and Gynecology, Clinical Research Developmental Unit, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Assistant Professor of Hematology & Oncology, Department of Internal Medicine, School of Medicine, Hazrat-E Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Hormozgan University of Medical Sciences, Hormozgan, Iran
  5. 5. Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
  6. 6. Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Indian Journal of Gynecologic Oncology Published:2025


Abstract

Objective: Ovarian cancer (OC) is a heterogeneous gynecological malignancy characterized by anatomical, molecular, and cellular diversity, contributing to variable responses to surgical and chemotherapeutic treatments. This complexity underlies its aggressive clinical behavior and rapid development of drug resistance. Emerging evidence highlights that tumor progression and metastasis are strongly influenced by interactions within the tumor microenvironment (TME). Aim and purpose: In this review, we comprehensively examine the contributions of platelet-leukocyte crosstalk in OC progression and evaluate the therapeutic potential of anti-platelet and anti-NET strategies. Materials and Methods: This study conduct based keywords including “platelet”, “leukocyte”, “ovarian cancer”, “signaling”. Also, the search done in pubmed and google scholar database. Results: As a result, modern immunotherapeutic strategies are increasingly focused on modulating the TME. Among these, platelet-leukocyte crosstalk has gained attention as a pivotal contributor to OC progression. Upon activation, platelets express Pselectin and release granules enriched with pro-inflammatory and immunomodulatory mediators, notably transforming growth factor-beta 1 (TGF-β1). P-selectin facilitates platelet-neutrophil aggregation, which triggers NETosis— a form of neutrophil cell death involving the release of neutrophil extracellular traps (NETs). This process amplifies thromboinflammation and sustains a pathological feedback loop of immune activation and suppression. Platelet-derived TGF-β1 further impairs anti-tumor immunity by promoting the polarization of N2-neutrophils and M2- macrophages, as well as enhancing regulatory T cell (Treg) differentiation within the TME. Additionally, elevated TGF- β1 levels at the tumor site drive epithelial-to-mesenchymal transition (EMT), contributing to metastasis. Together, these mechanisms underscore the critical role of platelet activation and platelet-leukocyte interactions in OC pathogenesis. Conclusion: Furthermore, to address the limitations of current treatments, we propose a novel approach utilizing pH-sensitive nanoparticles co-encapsulating anti-platelet agents and doxorubicin. This strategy enables targeted drug delivery to the acidic OC TME, enhancing therapeutic efficacy while minimizing systemic side effects. © The Author(s) under exclusive licence to Association of Gynecologic Oncologists of India 2025.
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