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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Inactivating mutations in genes encoding for components of the BAF/PBAF complex and immune-checkpoint inhibitor

Kevin Courtet1,2,3, Yec'han Laizet1,2, Carlo Lucchesi1,2

  • 1INSERM U1218, Bordeaux, France.

Biomarker Research
|July 23, 2020
PubMed

Insights

Mutations in BAF/PBAF complex genes are common in cancer and significantly improve survival for patients treated with immune-checkpoint inhibitors (ICI). These BAF/PBAF gene mutations are independent predictors of better outcomes in ICI therapy.

Area of Science:

  • Oncology
  • Cancer Genetics
  • Immunotherapy

Background:

  • Alterations in BAF/PBAF complexes are frequent in human cancers.
  • These genetic changes can influence the tumor microenvironment and response to immune-checkpoint inhibitors (ICI).

Purpose of the Study:

  • To investigate the association between mutations in key BAF/PBAF complex genes and patient outcomes in ICI therapy.

Main Methods:

  • Analysis of clinical and genetic data from 43,728 cancer patients via cBioportal.
  • Investigated mutations in ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1.
  • Assessed the impact of these mutations on overall survival in 1661 patients receiving ICI treatment using multivariable Cox regression analysis.

Main Results:

  • Mutational frequencies for ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1 were 6.6%, 3.4%, 3.4%, 3.2%, 4.1%, and 1.2%, respectively.
  • Patients with BAF/PBAF mutated tumors showed significantly improved overall survival (28 months vs. 15 months, p < 0.0001).
  • BAF/PBAF gene mutations were identified as an independent prognostic factor for overall survival in patients treated with ICI, even after adjusting for tumor mutational burden.

Conclusions:

  • Mutations in genes encoding BAF/PBAF complex components are linked to improved outcomes in patients receiving immune-checkpoint inhibitor therapy.
  • These findings highlight a significant relationship between BAF/PBAF complex gene status and ICI treatment efficacy.
  • Further research is warranted to elucidate the specific mechanisms underlying this observed interaction.
Keywords:
BAP/PBAF complexImmune checkpoint inhibitorsSWI/SNF complex

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