Work

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

Year: 2025

Type: article

Abstract: ABSTRACT 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 (IFNγ, IL‐6, and IL‐2). Treatment with anti‐CD3/CD28 increased the frequency of CD137 + /CD8 + T cells and induced cytokine responses dominated by IFNγ, IL‐2, and Granzyme B. While both non‐tumor and tumor‐border tissue responded to anti‐CD3/CD28, the intensities of immune responses were highly varied. Notably, treatment with Nivolumab induced an inflammatory response primarily in the tumor‐border evidenced by IFNγ, IL‐2, and Perforin secretion alongside increased expression of CD107a on CD8 + T cells, in a donor‐dependent manner. Taken together, these data demonstrate how tumor‐border tissue slices can be utilized to study T cell responses in the context of the patient‐specific tumor microenvironment.

Source: European Journal of Immunology

DOI: 10.1002/eji.70060