Development of a novel immune infiltration-based gene signature to predict prognosis and immunotherapy response of a novel anti-PD-L1/TGF-β bifunctional fusion protein in recurrent cervical cancer

The hypothesis-generating case study aimed at identifying those who are sensitive to anti-PD-L1 and TGF-β bifunctional fusion proteins and exploring potential mechanisms in the treatment of recurrent cervical cancer. We report that recurrent cervical cancer treated with anti-PD-L1 and TGF-β bifunctional fusion proteins in Qilu Hospital of Shandong University show distinct clinical therapeutic outcomes. We describe the clinical course, characteristics, and genetic characteristics of the patients and analyzed the differentially expressed genes (DEGs) following treatment. The elevation of peripheral blood lymphocytes after treatment may predict response to anti-PD-L1 and TGF-β bifunctional fusion proteins, since partial response (PR) and progressive disease (PD) exhibit different trends. A total of 4,844 DEGs were selected between PR and PD patients during the anti-PD-L1 and TGF-β bifunctional fusion protein treatments, which are believed to be involved in the regulation of the immune response. We demonstrated that changing-fate genes continuously change during treatment fostering the IL 17 signaling pathway and TGF-β signaling pathways. Finally, we identified the prognostic genes and validated that high expression levels of PMEPA1, FSTL3, SERPINE1, CXCL1, CXCL8, and low expression levels of JUND，MAP2K2 were significantly associated with poor prognosis of cervical cancer patients using the TCGA database. Anti-PD-L1 and TGF-β bifunctional fusion proteins are feasible and effective for recurrent cervical cancer through the IL 17 signaling pathway and TGF-β signaling pathways. A novel immune infiltration-based gene signature consisting of PMEPA1, FSTL3, SERPINE1, CXCL1, CXCL8, JUND, and MAP2K2 plays a crucial role in recurrent cervical cancer patients with anti-PD-L1 and TGF-β bifunctional fusion proteins.