Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells
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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.
KeywordsNon-small cell lung cancer Primary tumor Metastasis Immune cells Anti-tumor immunity
Non-small cell lung cancer
This work was supported by grants from the Swiss National Science Foundation, the Wilhelm Sander-Foundation, the Cancer League Basel, the Huggenberger-Bischoff Foundation for Cancer Research, the Research Fonds of the University Basel and the Freiwillige Akademische Gesellschaft Basel.
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Conflict of interest
The authors declare that they have no conflict of interest.
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