Data from <i>PTEN</i> Loss Shapes Macrophage Dynamics in High-Grade Serous Ovarian Carcinoma

• DOI: 10.1158/0008-5472.c.7541194
• Publication Date: 2024-11-15T08:24:41Z
• Authors: Sarah Spear; Olivia Le Saux; Hasan B. Mirza; Nayana Iyer; Katie Tyson; Fabio Grundland F...; Josephine B. Walton; Chloé Woodman; Sheba Jarvis; Darren P. Ennis; Carmen Aguirre He...; Yuewei Xu; Pavlina Spiliopoulou; James D. Brenton; Ana P. Costa-Pereira; David P. Cook; Barbara C. Vander...; Hector C. Keun; Evangelos Trianta...; James N. Arnold; Iain A. McNeish
• Keywords: Dynamics; Serous ovarian cancer

&lt;div&gt;Abstract&lt;p&gt;High-grade serous ovarian carcinoma (HGSC) remains a disease with poor prognosis that is unresponsive to current immune checkpoint inhibitors. Although PI3K pathway alterations, such as &lt;i&gt;PTEN&lt;/i&gt; loss, are common in HGSC, attempts target this have been unsuccessful. We hypothesized aberrant activation may alter the HGSC microenvironment and present targeting opportunity. Single-cell RNA sequencing identified populations of resident macrophages specific &lt;i&gt;Pten&lt;/i&gt;-null omental tumors murine models, which were confirmed by flow cytometry. These derived from peritoneal fluid exhibited unique gene expression program, marked high enzyme heme oxygenase-1 (HMOX1). Targeting prevented appearance HMOX1&lt;sup&gt;hi&lt;/sup&gt; reduced tumor growth. In addition, direct inhibition HMOX1 extended survival &lt;i&gt;in vivo&lt;/i&gt;. IL33 cells likely candidate driver, leading macrophages. Human also contained corresponding program. Moreover, presence these was correlated activated tumoral PI3K/mTOR signaling overall patients HGSC. contrast, low numbers increased adaptive response expression. data suggest potential therapeutic strategy for treating HGSC.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; Macrophages elevated enriched &lt;i&gt;PTEN&lt;/i&gt;-deficient high-grade carcinoma, promote growth, represent target.&lt;/p&gt;&lt;/div&gt;