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HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer

Christiane Gruetzmacher1, Bruna Sousa Pessoa1, Flora Ladeira Craveiro1

  • 1Neuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Endocrine Oncology (Bristol, England)
|April 21, 2025
PubMed
Abstract

Insights

Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2) shows varied roles in endocrine cancers. This immune checkpoint target may serve as a prognostic biomarker, with expression influencing patient outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), a B7 family member, is expressed in various human cancers.
  • HHLA2 is recognized as a potential immune checkpoint target for cancer therapy.
  • Its role in endocrine-related cancers requires further elucidation.

Purpose of the Study:

  • To consolidate existing data on HHLA2 expression in endocrine-related cancers.
  • To evaluate HHLA2 as a prognostic biomarker in these cancers.
  • To understand the dual functions of HHLA2 in the tumor microenvironment.

Main Methods:

  • Systematic literature search of PubMed, Web of Science, and Embase up to December 2024.
  • Inclusion criteria focused on studies of HHLA2 in endocrine-related cancers.
  • Search terms included 'HHLA2', 'B7-H7', 'B7y', 'B7-H5', and relevant cancer types.

Main Results:

  • Twelve studies met inclusion criteria from 117 reviewed.
  • Pancreatic cancer: varied HHLA2 expression, high levels linked to better prognosis.
  • Ovarian cancer: conflicting results on HHLA2 and survival; thyroid cancer and neuroendocrine tumors: HHLA2 associated with poor prognosis and metastasis.

Conclusions:

  • HHLA2 exhibits dual roles (immunosuppressive and tumor-suppressive) in endocrine-related tumors.
  • Tumor microenvironment may influence HHLA2 expression.
  • HHLA2 shows promise as an immune checkpoint biomarker and therapeutic target in oncology.
Keywords:
HHLA2biomarkercancer immunotherapyendocrine-related cancerimmune checkpointtherapeutic target

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