Development of a novel immune infiltration-based gene signature to predict prognosis and immunotherapy response

Sep 23, 2026

Uploaded by Margaret

A hypothesis-generating research study identifies sensitivity to anti-PD-L1 and TGF-β bifunctional fusion proteins and explores underlying mechanisms in recurrent cervical cancer. Distinct clinical therapeutic outcomes are reported for patients treated at Qilu Hospital of Shandong University, alongside profiling of differentially expressed genes after therapy. Peripheral blood lymphocyte elevation may predict response, with PR and PD showing different trends. A total of 4,844 DEGs differ between PR and PD, linked to immune regulation, and IL-17 and TGF-β signaling pathways are implicated.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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HUMAN VACCINES & IMMUNOTHERAPEUTICS 2026, VOL. 22, NO. 1, 2647560 [https://doi.org/10.1080/21645515.2026.2647560](https://doi.org/10.1080/21645515.2026.2647560) RESEARCH ARTICLE 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 Yucen Maoa*, Naidong Xingb*, Wenxiong Sunc*, Xinyue Baoa, Xihan Liua, Richao Wuc, and Jin Peng a aDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China; bDepartment of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China; cDepartment of Gynecology, Weifang People’s Hospital, Weifang, Shandong, China ABSTRACT The hypothesis-generating case study aimed at identifying those who are sensitive to antiPD-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. ARTICLE HISTORY Received 3 December 2025 Revised 5 March 2026 Accepted 14 March 2026 KEYWORDS Recurrent cervical cancer; anti-PD-L1/TGF-βRIIbifunctional fusion protein; tumor immunotherapy Introduction Cervical cancer, which develops through persistent infection with high-risk human papilloma virus, is the fourth most common cancer in terms of both incidence and mortality, and the leading cause of death among women worldwide. 1 With the popularization of cervical cancer vaccines and cervical cancer screening, the incidence and mortality rates of cervical cancer have decreased in many countries worldwide, and the World Health Organization (WHO) has set the goal of eliminating cervical cancer globally during the 21st century.2–4 For early stage cervical cancer, surgery is considered the primary treatment option, and most patients have a good prognosis; however, for women with metastatic or recurrent disease, the overall prognosis remains poor.5–9 New treatment modalities need to be developed, particularly for patients with chemotherapy intolerance. Programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors may be a novel choice to improve the clinical outcomes of recurrent cervical cancer. 10 PD-L1 is highly expressed in various malignant tumors such as breast cancer, cervical cancer, ovarian cancer, non-small-cell lung cancer, esophageal cancer, gas

FAQs

What is the main aim of the study on recurrent cervical cancer?

To identify patients sensitive to anti-PD-L1 and TGF-β bifunctional fusion proteins and to explore potential mechanisms behind their treatment effects.

How do the authors assess molecular differences after treatment?

They analyze differentially expressed genes (DEGs) following treatment and compare DEGs between partial response (PR) and progressive disease (PD) groups.

Which gene signature is reported as prognostic, and what is its reported role?

The study proposes an immune infiltration-based gene signature including PMEPA1, FSTL3, SERPINE1, CXCL1, CXCL8, JUND, and MAP2K2, associated with poor prognosis and linked to IL-17 and TGF-β signaling pathways.

Sep 23, 2026

Uploaded by Margaret