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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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Published on: March 7, 2025

The Steroidal Profile Modulates Adaptive Immune Response and Prognosis in Adrenocortical Carcinoma: Analysis of TCR

Jean Silva de Souza Resende1,2, Igor Samesima Giner1, João Carlos Degraf Muzzi1

  • 1Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Complexo Pequeno Príncipe, Curitiba, PR, Brazil.

Cancer Medicine
|June 6, 2026
PubMed

Insights

Steroid phenotype significantly impacts the immune response in adrenocortical carcinoma (ACC). Low steroid phenotype tumors show greater immune infiltration and diversity, suggesting a more immunogenic environment crucial for personalized immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Endocrinology

Background:

  • Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with poor prognosis and limited treatments.
  • Tumor heterogeneity in hormone production influences ACC's immune microenvironment.
  • Understanding T-cell receptor (TCR) and B-cell receptor (BCR) repertoires is vital for personalized ACC therapies.

Purpose of the Study:

  • To investigate the role of steroid phenotype in shaping the adaptive immune response in ACC.
  • To analyze the composition and prognostic significance of TCR and BCR repertoires in different ACC subtypes.
  • To explore the link between hormonal environment, immunobiology, and clinical outcomes in ACC.

Main Methods:

  • Classification of ACC tumors into high steroid phenotype (HSP) and low steroid phenotype (LSP) subtypes.
  • Analysis of lymphocytic infiltration and TCR/BCR repertoire diversity in ACC subtypes.
  • Correlation of immune repertoire characteristics with steroid phenotype and clinical outcomes.

Main Results:

  • Steroid phenotype is a key determinant of the adaptive immune response in ACC.
  • LSP tumors exhibit significantly higher lymphocytic infiltration and greater repertoire diversity than HSP tumors.
  • Despite immune evasion gene expression, LSP tumors present a more immunogenic microenvironment.

Conclusions:

  • Hormonal environment significantly shapes ACC immunobiology and immune escape mechanisms.
  • Immune repertoire characteristics, particularly TCR/BCR diversity, have prognostic relevance in ACC.
  • Integrating steroid phenotyping with TCR/BCR profiling can enhance risk stratification and guide precision immunotherapy for ACC.
Keywords:
immunoinformaticsimmunosuppressionprognosissteroidal phenotypetumor microenvironment

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