The effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon c
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ORIGINAL ARTICLE
The effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma Daniëlle Krijgsman1,2 · Natasja L. De Vries1,2,5 · Morten N. Andersen2,4 · Anni Skovbo2,3 · Rob A. E. M. Tollenaar1 · Esther Bastiaannet1 · Peter J. K. Kuppen1 · Marianne Hokland2 Received: 8 January 2020 / Accepted: 23 April 2020 © The Author(s) 2020
Abstract Objective The subset distribution and immunophenotype of circulating immune cells (“peripheral blood immune cell profile”) may reflect tumor development and response to cancer treatment. In order to use the peripheral blood immune cell profile as biomarker to monitor patients over time, it is crucial to know how immune cell subsets respond to therapeutic interventions. In this study, we investigated the effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma (CC). Methods The subset distribution and immunophenotype of T cells (CD3+CD56−), CD56dim NK cells (CD3−CD56dim), CD56bright NK cells (CD3−CD56bright) and NKT-like cells (CD3+CD56+) were studied in preoperative and postoperative peripheral blood mononuclear cell (PBMC) samples of 24 patients with CC by multiparameter flow cytometry. Changes in immunophenotype of circulating immune cells after tumor resection were studied in patients treated with and without (capecitabine-based) adjuvant therapy. Results The NKT-like cell (% of total PBMCs) and CD8+ T cell (% of total T cells) populations expanded in the peripheral blood of non-adjuvant-treated CC patients after surgery. NK- and NKT-like cells showed upregulation of activating receptors and downregulation of inhibitory receptors in non-adjuvant-treated CC patients after surgery. These changes were not observed in the peripheral blood of adjuvant-treated CC patients. Conclusions Our results suggest tumor-induced suppression of NK- and NKT-like cells in CC patients, an effect that could not be detected after tumor resection. In contrast, adjuvant therapy maintained tumor-induced immunosuppression of NKand NKT-like cells in CC patients. Keywords Colon carcinoma · Peripheral blood immune cell profile · Cancer immunology · Natural cytotoxicity receptors · Adjuvant therapy · Tumor resection
Peter J. K. Kuppen and Marianne Hokland are equally responsible for this study. * Peter J. K. Kuppen [email protected] 1
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
2
Department of Biomedicine, Aarhus University, Aarhus, Denmark
3
FACS Core Facility, Aarhus University, Aarhus, Denmark
4
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
5
Present Address: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Abbreviations CC Colon carcinoma CRC Colorectal cancer DNAM-1 DNAX accessory molecule-1 HLA Human leukocyte antigen LUMC Leiden University Medical Center MFI Median flu
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