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Objective <p>Chronic inflammation associated with infection has been implicated in prostate cancer (PCa) progression, yet the immunological mechanisms linking sexually transmitted pathogens to tumor development remain incompletely understood. <i>Trichomonas vaginalis</i> (Tv), the most prevalent nonviral sexually transmitted parasite worldwide, has been associated with prostatic inflammation and increased PCa risk. However, how Tv-induced inflammation influences tumor progression has not been clearly defined. Here, we investigated whether Tv-induced epithelial inflammation promotes Th17 differentiation and drives prostate tumor progression through intratumoral IL-17 receptor (IL-17R) signaling.</p> Methods <p>Conditioned media of prostate epithelial cells (PECs, RWPE-1 cell line) was prepared by infection without (CM) and with Tv (TCM). Human CD4<sup>+</sup> T cells were isolated using the CD4<sup>+</sup> isolation kit from human peripheral blood. Conditioned medium of CD4<sup>+</sup> T cells was prepared by incubation with CM (T-CM) or TCM (T-TCM).</p> Results <p>Conditioned media from Tv-stimulated PECs induced robust production of IL-6 and IL-1β, which promoted IL-6/IL-1R-dependent differentiation of human CD4⁺ T cells into Th17 cells. Conditioned media from these Th17 cells enhanced proliferation and migration of prostate epithelial and cancer cells and activated IL-17R-TRAF6-NF-κB signaling pathways. Using a syngeneic mouse prostate cancer model in C57BL/6 mice, we found that IL-17R neutralization significantly reduced tumor growth without affecting Th17 cell abundance, supporting the involvement of tumor-intrinsic IL-17R signaling in Tvs-associated tumor progression. Spatial transcriptomic analysis further revealed enrichment of IL-17R-associated proliferative and invasive gene programs in Tvs-treated tumors. Consistently, analysis of prostate adenocarcinoma datasets showed that IL17RA expression was associated with proliferative and invasive signatures and poorer clinical outcomes.</p> Conclusion <p>Collectively, these findings identify a Tv-Th17-IL-17R signaling axis linking infection-induced inflammation to tumor-intrinsic oncogenic signaling in prostate cancer, highlighting IL-17R signaling as a potential therapeutic target in inflammation-associated PCa.</p>

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Trichomonas vaginalis-induced inflammation is associated with Th17 differentiation and tumor-intrinsic IL-17R signaling in prostate cancer progression

  • 期刊论文

  • 发表日期：

    2026年6月29日

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  • Ik-Hwan Han,
  • Seobo Sim,
  • Juri Kim,
  • Soon-Jung Park,
  • Jae-Sook Ryu

摘要

Objective

Chronic inflammation associated with infection has been implicated in prostate cancer (PCa) progression, yet the immunological mechanisms linking sexually transmitted pathogens to tumor development remain incompletely understood. Trichomonas vaginalis (Tv), the most prevalent nonviral sexually transmitted parasite worldwide, has been associated with prostatic inflammation and increased PCa risk. However, how Tv-induced inflammation influences tumor progression has not been clearly defined. Here, we investigated whether Tv-induced epithelial inflammation promotes Th17 differentiation and drives prostate tumor progression through intratumoral IL-17 receptor (IL-17R) signaling.

Methods

Conditioned media of prostate epithelial cells (PECs, RWPE-1 cell line) was prepared by infection without (CM) and with Tv (TCM). Human CD4+ T cells were isolated using the CD4+ isolation kit from human peripheral blood. Conditioned medium of CD4+ T cells was prepared by incubation with CM (T-CM) or TCM (T-TCM).

Results

Conditioned media from Tv-stimulated PECs induced robust production of IL-6 and IL-1β, which promoted IL-6/IL-1R-dependent differentiation of human CD4⁺ T cells into Th17 cells. Conditioned media from these Th17 cells enhanced proliferation and migration of prostate epithelial and cancer cells and activated IL-17R-TRAF6-NF-κB signaling pathways. Using a syngeneic mouse prostate cancer model in C57BL/6 mice, we found that IL-17R neutralization significantly reduced tumor growth without affecting Th17 cell abundance, supporting the involvement of tumor-intrinsic IL-17R signaling in Tvs-associated tumor progression. Spatial transcriptomic analysis further revealed enrichment of IL-17R-associated proliferative and invasive gene programs in Tvs-treated tumors. Consistently, analysis of prostate adenocarcinoma datasets showed that IL17RA expression was associated with proliferative and invasive signatures and poorer clinical outcomes.

Conclusion

Collectively, these findings identify a Tv-Th17-IL-17R signaling axis linking infection-induced inflammation to tumor-intrinsic oncogenic signaling in prostate cancer, highlighting IL-17R signaling as a potential therapeutic target in inflammation-associated PCa.