Abstract 5524: Identification of PAEP as an immune activity modulator to mediate the immune resistance in tumor metastasis

Abstract

Abstract Most cancer-related deaths are associated with the complex phenotypic behavior of metastasis, a process in which tumor cells spread from their initial site to distant sites. To successfully metastasize, the tumor cell will be required to make numerous adjustments and survive a series of stages involving intravasation, circulation in the blood or lymph system, extravasation, and growth at distant organs, and overcome the challenges of immunosurveillance. The tumor microenvironment is the ecosystem that surrounds and feeds the tumor. The molecular mechanism by which the metastatic tumors survive and escape from immune attack in the tumor microenvironment remains unclear. To study the molecular mechanism of interaction between metastatic tumors and the immune system in metastasis, we established immune-resistant metastatic models. We identified that PAEP, a progestogen-associated endometrial protein, is significantly upregulated in immune-resistant metastatic tumors compared with non-immune-resistant tumors. PAEP is a glycoprotein that inhibits cell immune function and plays an essential role in the pregnancy process. To examine the function of PAEP in tumor metastasis, we first introduced PAEP into non-immune resistant and poorly metastatic melanoma and rhabdomyosarcoma (RMS) cells. We found that overexpression of PAEP significantly promotes tumor metastatic potential of both melanoma and RMS cells in immunocompetent mice. Interestingly, there was no difference in metastasis between the control and overexpression groups in immunodeficient mice. These data suggest that PAEP may mediate tumor metastasis relating to host immunity. To further confirm the function of PAEP in tumor metastasis, we use CRISPR/Cas9 technology to knockout endogenous PAEP and will test the metastatic potential in different hosts. We will also investigate the molecular mechanisms using RNA sequencing and Digital Spatial Profiling (DSP) to analyze the metastatic samples. Our study will uncover a new mechanism for how tumors survive in the microenvironment and identify a novel target for the treatment of metastatic diseases. Citation Format: Rand Gabriel M. Buenaventura, Weiping Chen, Shuling Zhang, Beverly Mock, Glenn Merlino, Yanlin Yu. Identification of PAEP as an immune activity modulator to mediate the immune resistance in tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5524.