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Temporal and spatial composition of the tumor microenvironment predicts response to immune checkpoint inhibition in metastatic TNBC - PubMed

4 days ago
  • #tumor microenvironment
  • #immune checkpoint inhibition
  • #triple-negative breast cancer
  • The study focuses on predicting response to immune checkpoint inhibition (ICI) in metastatic triple-negative breast cancer (TNBC) using tumor microenvironment analysis.
  • A longitudinal cohort of 103 patients from the TONIC trial was analyzed, including primary tumors, pretreatment metastases, and on-treatment metastases during nivolumab therapy.
  • Highly multiplexed imaging profiled 37 proteins in 270 tumors, and the SpaceCat pipeline extracted over 800 imaging features per sample.
  • Metastatic tumors, but not primary tumors, contained features predictive of ICI response, with spatial metrics like immune diversity and T cell infiltration at tumor borders being most informative.
  • Multivariate models achieved high performance in stratifying patients (AUC = 0.90), and bulk RNA-seq confirmed the predictive value of on-treatment samples.
  • The study highlights the importance of longitudinal profiling to understand evolving tumor microenvironment dynamics influencing ICI response.