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Acyl CoA binding protein (ACBP): an autophagy checkpoint that can be targeted for improving cancer immunosurveillance

Léa Montégut1,2, Isabelle Martins1,2, Guido Kroemer1,3

  • 1Team Metabolism, Cancer and Immunity, Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, Paris, France.

Oncoimmunology
|October 9, 2024
PubMed

Insights

Acyl CoA binding protein (ACBP) limits autophagy and acts as an extracellular checkpoint. Neutralizing ACBP with antibodies enhances cancer immunosurveillance and improves outcomes in preclinical chemoimmunotherapy models.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Acyl CoA binding protein (ACBP), encoded by the DB I gene, functions as a tissue hormone.
  • ACBP acts as an extracellular checkpoint, limiting autophagy in various cell types.
  • Previous research indicated ACBP neutralization enhances immunosurveillance in breast and lung carcinomas.

Purpose of the Study:

  • To investigate the therapeutic potential of ACBP neutralization in cancer.
  • To evaluate the impact of ACBP blockade on immunosurveillance and chemoimmunotherapy outcomes.

Main Methods:

  • Utilizing monoclonal antibodies to neutralize ACBP activity.
  • Assessing changes in autophagy levels and cancer cell immunosurveillance.
  • Evaluating treatment outcomes in preclinical models of breast and lung cancer undergoing neoadjuvant chemoimmunotherapy with PD-1 blockade.

Main Results:

  • ACBP neutralization was shown to improve cancer immunosurveillance.
  • The neutralization of ACBP enhanced the efficacy of neoadjuvant chemoimmunotherapy combined with PD-1 blockade in preclinical settings.
  • ACBP blockade demonstrated a positive impact on treatment outcomes in tested carcinoma models.

Conclusions:

  • ACBP is a critical regulator of autophagy and a potential target for cancer immunotherapy.
  • Antibody-mediated neutralization of ACBP represents a promising strategy to enhance anti-tumor immunity.
  • Targeting ACBP may improve the effectiveness of current cancer treatment modalities, including chemoimmunotherapy.
Keywords:
Caloric restriction mimeticschemotherapyimmune checkpoint inhibitorimmunotherapy mammary carcinomanon-small cell lung cancer

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