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journal article·2026-06-23Open access

Placental Site Trophoblastic Tumor Acquires Immune Functions by Incorporating Host Maternal Genes

Kyosuke Kagami, Masanori Ono, Yasunari Mizumoto, Tatsuhito Kanda, Takashi Iizuka, Takiko Daikoku, Shin‐ichi Horike, Akira Hattori, Akihito Horie, Sachiko Minamiguchi, Tomoko Fujiwara, Kazuyoshi Hosomichi, Atsushi Tajima, Hirokazu Usui, Kaoru Abiko, Hiroshi Fujiwara

Advanced Science
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Abstract

ABSTRACT Although it was proposed that cell fusion of cancer cells with leukocytes creates mobile hybrids with a metastatic phenotype, it has been difficult to genetically confirm cell fusion events in human cancer in vivo. Here, we experienced 4 cases of placental site trophoblastic tumor (PSTT) that produced immunoglobulin (Ig). Three cases showed recurrence and responded well to pembrolizumab therapy. Among them, we could analyze temporal changes in the genetic profiles on one case of daughter‐derived PSTT, which relapsed after pembrolizumab therapy. In this case, we found that PSTT incorporated the exogenous genes from host maternal cells. The rearrangement patterns of Ig genes and protein expressions sequentially increased. By analyzing single‐nucleotide variants, PSTT incorporated daughter‐non‐inherited maternal alleles (DNIMA), including the Ig lambda and HLA‐DQA2 loci. Protein expressions of TLR10 and SIGLEC10 increased during tumor progression concomitantly with DNIMA incorporation. DNIMA mapping indicates the incorporation of exogenous maternal genes was widely distributed through the whole chromosomes, suggesting the involvement of cell fusion in gene transfer mechanisms. These findings indicate that PSTT sequentially incorporated exogenous genes from maternal cells to express immune‐related molecules and suggest that cancer cells acquired B cell‐related functions, including Ig production by cell fusion with host immune cells.
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Research context

OpenAlex topics: Gestational Trophoblastic Disease Studies · Reproductive System and Pregnancy · Pregnancy and preeclampsia studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Obstetrics and Gynecology Graduate School of Medical Sciences Kanazawa University Kanazawa Japan

Department of Obstetrics and Gynecology Tokyo Medical University Shinjuku Tokyo Japan

Department of Obstetrics and Gynecology Keio University School of Medicine Shinjuku Tokyo Japan

Department of Obstetrics and Gynecology Ishikawa Prefectural Central Hospital Kanazawa Japan

Division of Animal Disease Model Research Center for Experimental Modeling of Human Disease Kanazawa University Kanazawa Japan

Division of Integrated Omics Research Research Center for Experimental Modeling of Human Disease Kanazawa University Kanazawa Ishikawa Japan

Department of System Chemotherapy and Molecular Sciences Kyoto University Graduate School of Pharmaceutical Sciences Kyoto Japan

Department of Gynecology and Obstetrics Kyoto University Graduate School of Medicine Kyoto Japan

Department of Obstetrics and Gynecology Medical Research Institute KITANO HOSPITAL Osaka Japan

Department of Diagnostic Pathology Fujita Health University School of Medicine Aichi Japan

Department of Human Life Environments Kyoto Notre Dame University Kyoto Japan

Laboratory of Computational Genomics School of Life Science Tokyo University of Pharmacy and Life Sciences Hachioji Tokyo Japan

Department of Bioinformatics and Genomics Graduate School of Advanced Preventive Medical Sciences Kanazawa University Kanazawa Japan

Department of Obstetrics and Gynecology Reproductive Medicine Chiba University Graduate School of Medicine Chiba Japan

Ochi Yume Clinic Nagoya Nagoya Japan

School of Veterinary Medicine Azabu University Sagamihara Japan

Funding

Japan Agency for Medical Research and Development

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