Characterizing Postoperative T and B Cell Dysfunction in Cancer Surgery Patients, Using COVID-19 as a Model Antigen
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Quantify the degree and determine the postoperative time course of antigen-specific T cell dysfunction following surgery
研究概览
简要总结
The Auer Lab research program studies how surgery affects the immune system and how this can lead to suppression in cancer patients which can lead to cancer reoccurrence. This has been well characterized in literature, with a clear demonstration that both surgery induced suppression of T cell and Natural Killer (NK) cell result in cancer recurrence..
The present study is the first in humans, to our knowledge, to demonstrate antigen specific dysfunction in T cells and B cells following cancer surgery. The study capitalized on the widespread vaccination of cancer patients against COVID before surgery, which allowed us to measure the response to the antigen S protein of SARS-CoV2. While the study is translational in methodology, we believe it will be of significant interest to all surgeons because it clearly establishes that surgery profoundly suppresses antigen-specific T and B cell responses, which have implications for postoperative infectious complications and cancer recurrence for those patients undergoing tumor resection
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a diagnosis of a primary abdominal malignancy consented to undergo major surgery with a planned length of stay of 3 or more days.
- •Eligible patients must have signed a consent for surgical resection of the malignancy.
- •Adequate hematological function defined as: platelet count ≥ 100 x 109/L, absolute neutrophil count ≥ 1 x 109/L, white blood count ≥ 2.5 x 109/L, hemoglobin count ≥ 90 g/L.
- •Adequate organ functioning, including: total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST, ALT < 2.5 x ULN; INR <1.5 ; CrCl>30mL/min.
- •Ability to understand and provide a signed informed consent form (ICF) approved by the Institutional Review Board (IRB/IEC/REB).
- •Ability to comply with protocol requirements.
排除标准
- •Documented significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids, azathioprine, cyclosporin A). Subjects may be on physiologic doses of replacement prednisone or equivalent doses of corticosteroid (<7.5 mg daily).
- •History of autoimmune disease (even if controlled with medication) such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.
- •Allergies or any contraindication to the use of tadalafil or any components of Cialis® or the influenza vaccine (including eggs), Agriflu®.
- •Serious intercurrent chronic or acute illness, or other illness considered by the investigator as an unwarranted high risk for an investigational product.
- •Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
- •Patients with resting hypotension (BP <90/50 at rest) or hypertension (BP >170/110 at rest).
- •Patients with cardiac failure or coronary artery disease causing unstable angina.
结局指标
主要结局
Quantify the degree and determine the postoperative time course of antigen-specific T cell dysfunction following surgery
时间窗: measured at day 0,1, 3, 28 post surgery
Used the production of IFNγ, as measured by ELISpot, to determine the degree and duration of surgery-induced suppression of T cell responses to the RBD antigen.
Characterize the phenotype of dysfunctional CD8+ T cells in the immediate postoperative period
时间窗: measured at day 0,1 post surgery
Using multicolor flow cytometry, we characterized the cell surface markers, intracellular pathways and cytokines that are altered on POD1 in CD8+ T cells in response to RBD antigen.
次要结局
未报告次要终点