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Benzodiazepines compromise the outcome of cancer immunotherapy

Léa Montégut1,2, Lisa Derosa3,4, Meriem Messaoudene5,6

  • 1Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Paris, France.

Oncoimmunology
|October 9, 2024
PubMed

Insights

Benzodiazepines, like diazepam, may suppress the immune system, counteracting cancer chemoimmunotherapy. This effect was observed in mice and linked to poor clinical responses in lung cancer patients treated with benzodiazepines.

Area of Science:

  • Immunology
  • Pharmacology
  • Oncology

Background:

  • Acyl CoA binding protein (ACBP/DBI) is an endogenous immunosuppressor.
  • ACBP/DBI and benzodiazepines modulate the GABA-A receptor.
  • Neutralizing ACBP/DBI enhances cancer immunotherapy efficacy in mouse models.

Purpose of the Study:

  • To investigate if diazepam administration reverses the beneficial effects of ACBP/DBI neutralization in cancer chemoimmunotherapy.
  • To determine if diazepam exhibits immunosuppressive properties.

Main Methods:

  • Administered diazepam to mice undergoing anti-ACBP/DBI antibody treatment for cancer chemoimmunotherapy.
  • Analyzed clinical responses in non-small cell lung cancer (NSCLC) patients receiving benzodiazepines versus other psychotropic drugs or no psychotropic drugs during chemoimmunotherapy.

Main Results:

  • Diazepam abolished the therapeutic effects of anti-ACBP/DBI antibodies in mice.
  • Benzodiazepine treatment in NSCLC patients was associated with poorer chemoimmunotherapy outcomes compared to patients not on psychotropic drugs.
  • Other psychotropic medications did not impact chemoimmunotherapy outcomes, suggesting a benzodiazepine-specific effect.

Conclusions:

  • Diazepam exerts immunosuppressive properties that can negate the immunostimulatory effects of ACBP/DBI neutralization.
  • Benzodiazepines may confer systemic immunosuppression, potentially compromising cancer chemoimmunotherapy efficacy.
  • Further epidemiological and clinical studies are needed to confirm the immunosuppressive role of benzodiazepines.
Keywords:
BenzodiazepinesImmunotherapycomedicationsneuroendocrine factorsnon-small cell lung cancer

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