Science and Research

Activation of CD8⁺ T Cells in the Human Ex Vivo Lung Tumor Microenvironment Using Anti-CD3/CD28 and Nivolumab

Despite advancements in immunotherapies, the diversity of the tumor microenvironment remains a challenge for cancer treatment. To elucidate microenvironment-specific differences in antitumor responses, we established patient-derived ex vivo tumor-lung slices. We analyzed immune activation profiles after treatment with anti-CD3/CD28 and the checkpoint inhibitor Nivolumab. Lung slices from non-tumor, tumor-adjacent, tumor-border, and tumor-central tissue were generated and assessed for viability, cell composition, and immune competence via flow cytometry, soluble factor secretion, and bulk RNA-sequencing. The tumor-border contained the highest number of immune cells (8.3-fold vs. non-tumor), secreted tumor markers (S100 and CA15-3), and exhibited high levels of inflammatory mediators (IFN

  • Bargmann, T.
  • Konzok, S.
  • Liguori, R.
  • Fuchs, M.
  • Sommer, C.
  • Schaudien, D.
  • Schob, C.
  • Halle, S.
  • Werlein, C.
  • Zardo, P.
  • Neubert, L.
  • Jonigk, D.
  • Fieguth, H. G.
  • Ferrazzi, F.
  • Sewald, K.
  • Dehmel, S.
  • Braun, A.

Keywords

  • Humans
  • *Tumor Microenvironment/immunology/drug effects
  • *Nivolumab/pharmacology
  • *CD8-Positive T-Lymphocytes/immunology/drug effects
  • *Lung Neoplasms/immunology/drug therapy/pathology
  • CD28 Antigens/immunology
  • CD3 Complex/immunology
  • *Lymphocyte Activation/drug effects/immunology
  • Immune Checkpoint Inhibitors/pharmacology
  • Female
  • Cytokines/metabolism
  • Male
  • CD8+ T cell responses
  • ex vivo models
  • immunotherapy
  • lung cancer
  • patient‐derived
  • tumor border
  • tumor lung slices
  • tumor microenvironment
Publication details
DOI: 10.1002/eji.70060
Journal: Eur J Immunol
Pages: e70060 
Number: 9
Work Type: Original
Location: BREATH
Disease Area: LC
Partner / Member: ITEM, MHH
Access-Number: 40952312


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