Chaoyang Zhang1, Feng Li2, Jieyao Li3, Yujie Xu4, Liping Wang5, Yi Zhang6. 1. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Department of Rheumatology, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, PR China. 2. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China. 3. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China. 4. Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan, PR China. 5. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China. Electronic address: wlp@zzu.edu.cn. 6. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, PR China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, PR China. Electronic address: yizhang@zzu.edu.cn.
Abstract
BACKGROUND: Lung tumor is a major cause of cancer incidence and patient death. Chemotherapy is the primary therapy used to treat lung cancer. In addition to direct cytotoxic effect on tumor cells, chemotherapeutic drugs activate immune responses to exert antitumor function. Here, the effects of docetaxel on the inhibitory molecules, programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (TIM-3) in T lymphocytes were explored in patients with lung adenocarcinoma. PATIENTS AND METHODS: Peripheral blood mononuclear cells were isolated from lung adenocarcinoma patients receiving cisplatin-docetaxel chemotherapy. By flow cytometry and PCR, the expressions of CTLA-4, PD-1 and TIM-3 in T cell subsets were analyzed. Health subjects were used as control group. RESULTS: During chemotherapy, suppressive markers were down-regulated in peripheral CD4+ and CD8+ T cells from patients with partial remission or stable disease. Additionally, interferon-γ production was also augmented during this period. In vitro assay showed that docetaxel reduced the expression of PD-1 on T-cell subsets without altering cell death. Further tests in Jurkat T cells demonstrated that docetaxel activated signal transduction and activator of transcription 3 (STAT3) signaling to suppress PD-1 expression, whereas STAT3 inhibition reversed the down-regulation of PD-1. CONCLUSION: Our data support the hypothesis that chemotherapeutic drugs are not only purely cytotoxic but are also immune modulators.
BACKGROUND: Lung tumor is a major cause of cancer incidence and patient death. Chemotherapy is the primary therapy used to treat lung cancer. In addition to direct cytotoxic effect on tumor cells, chemotherapeutic drugs activate immune responses to exert antitumor function. Here, the effects of docetaxel on the inhibitory molecules, programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (TIM-3) in T lymphocytes were explored in patients with lung adenocarcinoma. PATIENTS AND METHODS: Peripheral blood mononuclear cells were isolated from lung adenocarcinoma patients receiving cisplatin-docetaxel chemotherapy. By flow cytometry and PCR, the expressions of CTLA-4, PD-1 and TIM-3 in T cell subsets were analyzed. Health subjects were used as control group. RESULTS: During chemotherapy, suppressive markers were down-regulated in peripheral CD4+ and CD8+ T cells from patients with partial remission or stable disease. Additionally, interferon-γ production was also augmented during this period. In vitro assay showed that docetaxel reduced the expression of PD-1 on T-cell subsets without altering cell death. Further tests in Jurkat T cells demonstrated that docetaxel activated signal transduction and activator of transcription 3 (STAT3) signaling to suppress PD-1 expression, whereas STAT3 inhibition reversed the down-regulation of PD-1. CONCLUSION: Our data support the hypothesis that chemotherapeutic drugs are not only purely cytotoxic but are also immune modulators.
Authors: Rebecca M O' Brien; Jason McGrath; Noel E Donlon; Maria Davern; Ashanty M Melo; Croí E Buckley; Andrew D Sheppard; John V Reynolds; Niamh Lynam-Lennon; Stephen G Maher; Joanne Lysaght Journal: Sci Rep Date: 2022-02-28 Impact factor: 4.379