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

Satomi Hattori1, Nobuhisa Yoshikawa2, Wenting Liu3

  • 1Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan.

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Summary

Endometrial cancer immunophenotypes, defined by CD8-positive tumor-infiltrating lymphocytes (TILs), correlate with molecular subtypes and patient prognosis. Understanding these patterns can guide personalized immunotherapy strategies.

Keywords:
Endometrial cancerImmunophenotypePersonalized immunotherapyProMisE classificationTumor-infiltrating lymphocyte

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Endometrial cancer (EC) exhibits diverse molecular subtypes.
  • Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive cells, play a crucial role in the anti-tumor immune response.
  • The relationship between EC molecular subtypes and immune microenvironment characteristics remains incompletely understood.

Purpose of the Study:

  • To investigate the association between CD8-positive TIL distribution patterns (immunophenotypes) and the molecular subtypes of endometrial cancer.
  • To determine if these immunophenotypes correlate with patient prognosis.
  • To explore molecular factors influencing immunophenotype development.

Main Methods:

  • Analysis of two EC patient cohorts (n=145) classified by the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut, MMRd, NSMP, and p53abn.
  • Immunohistochemical staining and image analysis to quantify CD8-positive TILs in tumor centers and invasive margins.
  • RNA-sequencing (RNA-seq) to identify molecular drivers of immunophenotypes.

Main Results:

  • Three distinct immunophenotypes (inflamed, excluded, desert) were identified based on CD8-positive TIL patterns.
  • The inflamed phenotype was common in POLEmut and MMRd subtypes; the desert phenotype predominated in NSMP.
  • All p53abn tumors displayed non-inflamed phenotypes. Non-inflamed phenotypes correlated with poorer prognosis.
  • RNA-seq revealed enrichment of MYC target genes in non-inflamed MMRd/NSMP subtypes and type-1 interferon response genes in non-inflamed NSMP subtypes.

Conclusions:

  • Immunophenotype assessment, alongside molecular classification, can enhance personalized immunotherapy for EC.
  • Further research into the mechanisms underlying these immunophenotypes may reveal novel immunotherapy targets.