npj Precision Oncology (Jun 2024)

Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome

  • Dan Zhao,
  • Haiqing Li,
  • Isa Mambetsariev,
  • Tamara Mirzapoiazova,
  • Chen Chen,
  • Jeremy Fricke,
  • Deric Wheeler,
  • Leonidas Arvanitis,
  • Raju Pillai,
  • Michelle Afkhami,
  • Bihong T. Chen,
  • Martin Sattler,
  • Loretta Erhunmwunsee,
  • Erminia Massarelli,
  • Prakash Kulkarni,
  • Arya Amini,
  • Brian Armstrong,
  • Ravi Salgia

DOI
https://doi.org/10.1038/s41698-024-00626-6
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 12

Abstract

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Abstract We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68+ cells and FOXP3+ cells being associated with response or resistance to ICIs were also identified. In particular, CD68+ cells, CD33+ and FOXP3+ cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68dim cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.