Understanding the impact of spatial immunophenotypes on the survival of endometrial cancer patients through the ProMisE classification.

Autor: Hattori S; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Yoshikawa N; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan. n-yoshikawa@med.nagoya-u.ac.jp., Liu W; Department of Obstetrics and Gynecology Collaborative Research, Bell Research Center, Nagoya University Graduate School of Medicine, Nagoya, Japan., Matsukawa T; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Kubokawa M; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Yoshida K; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Yoshihara M; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Tamauchi S; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Ikeda Y; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Yokoi A; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Shimizu Y; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Niimi K; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan., Kajiyama H; Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2025 Jan 03; Vol. 74 (2), pp. 70. Date of Electronic Publication: 2025 Jan 03.
DOI: 10.1007/s00262-024-03919-8
Abstrakt: Objectives: We focused on how the immunophenotypes based on the distribution of CD8-positive tumor-infiltrating lymphocytes (TILs) relate to the endometrial cancer (EC) molecular subtypes and patients' prognosis.
Patients and Methods: Two cohorts of EC patients (total n = 145) were analyzed and categorized using the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut (POLE mutation), MMRd (mismatch repair deficiency), NSMP (no specific molecular profile), and p53abn (p53 abnormality). CD8-positive TILs, within the central tumor and the invasive margin, were examined by using immunohistochemical staining and advanced image-analysis software. It was investigated whether these immunophenotypes correlate with the molecular subtypes and patients' survival. RNA-sequencing (RNA-seq) was used to explore tumor-derived factors influencing these immunophenotypes.
Results: Three distinct immunophenotypes (inflamed, excluded, and desert) based on the CD8-positive TIL patterns were identified in EC patients. Notably, the inflamed phenotype was most frequently observed in the POLEmut and MMRd subtypes, while the desert phenotype was predominant in the NSMP subtype; however, other immunophenotypes were also observed. All p53abn subtype showed the non-inflamed (excluded or desert) phenotype. The prognosis was markedly poorer in the patients with the non-inflamed phenotype than in those with the inflamed phenotype. The RNA-seq analysis showed that the expression of MYC target genes and type-1 interferon response genes was enriched in the non-inflamed phenotype in MMRd and NSMP subtypes, respectively.
Conclusion: Evaluating not only the molecular classification but also the immunophenotype may lead to more personalized immunotherapy in EC and elucidating the mechanisms that underlie the formation of the three immunophenotypes could lead to the discovery of new immunotherapy targets.
Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Consent to participate: Prospective cohort: All participants providing written informed consent. Retrospective cohort: An informational summary was presented on our hospital's website and the patients who did not consent were excluded. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Nagoya University (2018–0400).
(© 2024. The Author(s).)
Databáze: MEDLINE
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