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Abstract Breast cancer, a prevalent form of cancer worldwide, poses significant risks to women’s health. The interplay between cancer cells and their surrounding environment is pivotal in disease progression, facilitating tumor development and metastasis. Angiogenesis, the development of new blood vessels is a crucial process that is fueled by a complex nature of growth factors, chemokines, and cytokines in the tumor microenvironment (TME). Cytokines and chemokines play key roles in cancer development, orchestrating immune cell recruitment and communication within the TME. Interleukin-17 (IL-17), a proinflammatory cytokine primarily generated by T helper 17 (Th17) cells, and chemokine C-C Ligand 20 (CCL20), which attracts and guides immune cells, are implicated in breast cancer progression. So, the current study aimed at investigating the anti -tumor effect of IL- 17 and chemokine CCL20 antibodies through evaluating their effects on the angiogenic activity in breast cancerTME. Twenty Egyptian females undergoing modified radical mastectomy for histologically confirmed breast cancer were enrolled in the current study. Tissue samples from primary breast tumors and tumors apart normal tissue were cultured with and without anti-IL17 and anti-CCL20 antibodies. Angiogenesis was assessed using immunofluorescent technique to detect CD31 expression as specific marker of angiogenesis. Results: Spontaneous angiogenesis according to detected level of CD31 expression were significantly higher in untreated breast tumor tissue cultures compared to their current normal tissue. Neutralizing either IL-17 or CCL20 with their specific antibodies further decreased angiogenic activity in all tissue culture systems created in the study. The current study reveals several statistically significant correlations between breast tissue samples untreated and treated with anti-IL-17 or anti-CCL20 antibodies. Notably, normal breast tissues treated with either anti-IL-17 or anti-CCL20 Abs and core tumor breast tissues treated with anti-CCL20 Abs show statistically significant correlations with untreated normal and core tumor tissues, but not with peripheral tumor tissues. However, there is no significant relationship between tissues treated with anti-IL-17 Abs and those treated with anti-CCL20 Abs except a correlation between normal tissues treated with anti-IL-17 Abs and both normal and core tumor tissues treated with anti-CCL20 Abs. No significant correlations were found between CD31 expression and almost all clinicopathological parameters. However, anti-IL-17 Abs treatment showed a correlation with patients’ age in peripheral tumor tissue culture system and treatment with anti-CCL20 Abs showed a significant relationship with TNM classification in normal breast tissue culture system. Overall, targeting IL-17 or CCL20 with their specific antibodies could be promising immunotherapeutic approaches to reduce angiogenic activity in breast cancer. |