Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells

Muller, Philipp and Rothschild, Sacha I. and Arnold, Walter and Hirschmann, Petra and Horvath, Lukas and Bubendorf, Lukas and Savic, Spasenija and Zippelius, Alfred. (2016) Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells. Cancer Immunology Immunotherapy, 65 (1). pp. 1-11.

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Official URL: https://edoc.unibas.ch/62544/

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Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin-embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunology and Biology (Zippelius/Rochlitz)
UniBasel Contributors:Zippelius, Alfred
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1432-0851 (Electronic) 0340-7004 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Dec 2018 11:25
Deposited On:22 Dec 2018 11:25

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