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Sci Rep. 2019 Feb 22;9(1):2636. doi: 10.1038/s41598-019-39345-5.

Peripheral T cell cytotoxicity predicts T cell function in the tumor microenvironment.

Author information

1
Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. iwahori@climm.med.osaka-u.ac.jp.
2
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. iwahori@climm.med.osaka-u.ac.jp.
3
Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
4
Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
5
Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
6
Department of Frontier Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
7
Department of Pathology (Medical Research Center), Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
8
Department of Bone Marrow Transplant and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
9
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Abstract

Cancer immunotherapy, including immune checkpoint inhibitors, exerts beneficial effects in cancer patients. However, immune checkpoint inhibitors are only advantageous for a limited population of cancer patients. Therefore, companion diagnostics are needed in order to identify patients for whom these therapies are effective. In the present study, we evaluated detailed immunological aspects in clinical specimens from non-small cell lung cancer (NSCLC) patients. We analyzed the immune profiles, T cell cytotoxicity, and TCR repertoire of peripheral blood, normal lung tissue, and tumor tissue from NSCLC patients. By using bispecific T-cell engager technology to assess the cytotoxicity of T cells, we found that the cytotoxicity of tumor-infiltrated T cells closely correlated with that of peripheral T cells. This correlation was supported by the immune profiles, cytokine production, and results of the TCR repertoire analysis from these specimens. We also found that the cytotoxicity of peripheral T cells has potential as a predictor of the effects of nivolumab in the tumor microenvironment. These results imply further applications to blood-based immune monitoring systems and predictive biomarkers for cancer immunotherapy.

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