Abstract
BackgroundCholangiocarcinoma (CCA) is a highly aggressive and fatal tumor. CCA occurs in the epithelial cells of bile ducts. Due to increasing incidences, CCA accounts for 3% of all gastrointestinal malignancies. In addition to comprehensive treatments for cancer, such as surgery, chemotherapy, and radiotherapy, during the past few years, cellular immunotherapy has played an increasingly important role. As a result of our research, we have discovered the γδ T cell-based immunotherapy for CCA.Case presentationA 30-year-old male (https://www.clinicaltrials.gov/ ID: NCT02425735) was diagnosed with recurrent mediastinal lymph node metastasis after liver transplantation because of Cholangiocarcinoma (stage IV). In the course of his therapy sessions, he only received allogenic γδ T cell immunotherapy from August, 2017 through February, 2018 (8 infusions in total). γδ T cells were expanded from peripheral blood mononuclear cells (PBMCs) of healthy donor, and ~ 4 × 108 cells were adoptive transferred to the patient.ConclusionIn the above case report of the Cholangiocarcinoma (stage IV) patient who had received liver transplantation and afterward was diagnosed with recurrent mediastinal lymph node metastasis, we clinically proved that allogenic γδ T cell treatment had no adverse effects. We observed that allogenic γδ T cell treatments positively regulated peripheral immune functions of the patient, depleted tumor activity, improved quality of life, and prolonged his life span. After 8 γδ T cell treatments, the size of lymph nodes was remarkably reduced with activity depletion. This clinical work suggested that allogenic γδ T cell immunotherapy could be developed into a promising therapy drug for CCA.
Highlights
Cholangiocarcinoma (CCA) is the most common malignancy of the biliary tree; it may cause fatal consequences in a short period of time [1,2,3]
Our work provided the first paradigm on using allogenic γδ T cells to treat cancer
The results showed that γδ T cell therapy could greatly improve immunity by regulating the immunological functions of these immune cells, as the administration of γδ T cells was associated with an increase of the functional CD3 + CD4 + CD28+ T cells and CD3 + CD8 + CD28+ T cells, and decrease of CD3 + CD4 + CD28- T cells and CD3 + CD4 + CD28-CD57+ T cells
Summary
Cholangiocarcinoma (CCA) is the most common malignancy of the biliary tree; it may cause fatal consequences in a short period of time [1,2,3]. Because of poor efficacy results and prognoses of existing treatments for malignant cancer, the most up-to-date treatments are continually being researched, or under clinical trials. Immune cell therapy is emerging as an important alterative for malignant cancer treatment, after the success of Alnaggar et al Journal for ImmunoTherapy of Cancer. For all existing adoptive immune cell therapy, autologous T cells were applied because of MHC restriction. There have been no reports concerning allogenic T cell applications regarding clinical safety or efficacy. As a result of our research, we have discovered the γδ T cell-based immunotherapy for CCA. Case presentation: A 30-year-old male (https://www.clinicaltrials.gov/ ID: NCT02425735) was diagnosed with recurrent mediastinal lymph node metastasis after liver transplantation because of Cholangiocarcinoma (stage IV). In the course of his therapy sessions, he only received allogenic γδ T cell immunotherapy from August, 2017 through February, 2018 (8 infusions in total). γδ T cells were expanded from peripheral blood mononuclear cells (PBMCs) of healthy donor, and ~ 4 × 108 cells were adoptive transferred to the patient
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