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

Scientific Reports
Kota IwahoriHisashi Wada

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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Citations

Jul 7, 2019·Cancers·Takehiro OtoshiYoshihiro Nishimura
Apr 23, 2020·Frontiers in Pharmacology·Luisa Chocarro de ErausoDavid Escors
Jul 8, 2020·Cancers·Magalie DossetMaurizio Zanetti
Sep 19, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Theresa A ProiaPatricia McCoon
Jul 13, 2021·Frontiers in Oncology·Jin-Zhi LaiQiu-Yu Zhang
Oct 2, 2021·Journal of the National Cancer Institute·Annette M MolinaroJennifer L Clarke

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Methods Mentioned

BETA
flow cytometry
biopsy
FACS
Assay
PCR

Software Mentioned

RG
JMP
FACSDiva
MICE
Cluster
TreeView
R
BiTE

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