Chemotherapy as a double-edged sword: Modulation of tumor-associated cytokine and chemokine responses in ovarian cancer.

Abstract

Ovarian cancer (OC) is one of the most lethal gynecological malignancies, with high recurrence rates and chemoresistance posing significant challenges to effective treatment. Platinum-based agents, such as cisplatin and carboplatin, along with taxanes, including paclitaxel and docetaxel, represent fundamental therapies for OC. However, the immunomodulatory effects of these agents on the tumor microenvironment are multifaceted and can be perceived as a double-edged sword. Chemotherapeutics not only trigger cytotoxic effects but also influence the networks of pro- and anti-tumor cytokines, playing a role in both treatment efficacy and resistance. We specifically examine cytokine-mediated mechanisms underlying both platinum-based and taxane-based chemoresistance in OC. In this review, we comprehensively examine how platinum and taxane chemotherapy modulate cytokine signaling in OC, focusing on key mediators like interleukin (IL) 6, IL-8, transforming growth factor-beta, and C-X-C motif ligand 2 that drive survival pathways and chemoresistance. Interestingly, these agents might enhance anti-tumor immunity via interferon-gamma and IL-12, revealing the potential for synergistic chemoimmunotherapy. This research provides valuable insights for addressing resistance and improving combination therapies through the analysis of the dual roles of chemotherapy in modulating cytokine dynamics in OC.