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Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome.
Zhao, Dan; Li, Haiqing; Mambetsariev, Isa; Mirzapoiazova, Tamara; Chen, Chen; Fricke, Jeremy; Wheeler, Deric; Arvanitis, Leonidas; Pillai, Raju; Afkhami, Michelle; Chen, Bihong T; Sattler, Martin; Erhunmwunsee, Loretta; Massarelli, Erminia; Kulkarni, Prakash; Amini, Arya; Armstrong, Brian; Salgia, Ravi.
Affiliation
  • Zhao D; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Li H; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mambetsariev I; Integrative Genomic Core, Beckman Research Institute of City of Hope, Duarte, CA, USA.
  • Mirzapoiazova T; Department of Computational & Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA.
  • Chen C; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Fricke J; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Wheeler D; Department of Applied AI & Data Science, City of Hope, Duarte, CA, USA.
  • Arvanitis L; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Pillai R; Department of Human Oncology, University of Wisconsin, Madison, WI, USA.
  • Afkhami M; Department of Pathology, City of Hope, Duarte, CA, USA.
  • Chen BT; Department of Pathology, City of Hope, Duarte, CA, USA.
  • Sattler M; Department of Pathology, City of Hope, Duarte, CA, USA.
  • Erhunmwunsee L; Department of Diagnostic Radiology, City of Hope, Duarte, CA, USA.
  • Massarelli E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Kulkarni P; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Amini A; Department of Surgery, City of Hope, Duarte, CA, USA.
  • Armstrong B; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Salgia R; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
NPJ Precis Oncol ; 8(1): 135, 2024 Jun 19.
Article in En | MEDLINE | ID: mdl-38898200
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: NPJ Precis Oncol Year: 2024 Document type: Article Affiliation country: United States Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: NPJ Precis Oncol Year: 2024 Document type: Article Affiliation country: United States Country of publication: United kingdom