Effect of Anesthesia on Expression of Programmed Death-1 and Programmed Death-1 Ligand in Breast Cancer

Effect of Anesthesia on Expression of Programmed Death-1 and Programmed Death-1 Ligand in Breast Cancer

Effect of Anesthesia and Surgical Stress on the Expression of Programmed Death-1 and Programmed Death-1 Ligand on T Lymphocyte After Breast Cancer Surgeries

Surgery is first-line treatment for solid tumors. However, surgical trauma-induced physiologic stress has been demonstrated to facilitate metastasis and recurrence in different types of cancer. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.

The cellular immune response plays a central part in postoperative clearance of tumor cells. T lymphocytes and natural killer (NK) cells are two predominant cytotoxic effector cells that are the major components of antitumor immunity. In mouse models, proliferation of T lymphocytes in response to surgical trauma is defective . Programmed death-1 (PD-1) belongs to the CD28 receptor superfamily. It is an inhibitory receptor, and its expression is upregulated on activated leukocytes, resulting in an inhibited immune response. PD-1 interacts with two ligands: programmed death ligand-1 (PD-L1, also referred to as B7-H1) and programmed death ligand-2 (PD-L2, also known as B7-DC). PD-L2 is expressed mainly on activated dendritic cells (DCs) and macrophages, whereas PD-L1 is distributed widely. In addition to immune cells, some subsets of tumor cells also express PD-L1 to escape from immunosurveillance. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.

all patients will receive general anesthesia and will receive intravenous paracetamol (1 g) before skin closure and then given every 6 hrs in the 1st postoperative day

Patients will receive total volume (20 ml) 0.25% bubivicaine divided equally at each level of T4 and T6 at thoracic paravertebral space then they will recive general anesthesia.

TPVB will be given using high frequency linear U/S transducer, place the U/S ultrasound probe was placed parallel to the vertebral spine at T4, and, T6 level and shifted 2-3 cm laterally to obtain the appropriate visualization. Following the identification of pleura, transverse process and paravertebral space, the needle was inserted in caudocranial direction using in-plane approach. Confirm negative vessel or pleural breach via aspiration then proceed with local anaesthetic 0.25% bupivacaine (20 ml) delivery slowly divided equally at T4and T6; the pleura will be seen to be pushed downward

blood sample will be withdrawn and human peripheral blood monocyte cells (PBMCs) will be separated with a Ficoll-Isopaque density gradient. Flow cytometric analyses will be carried out immediately. For ex vivo experiments, PBMCs will be cultured with Iscove's modified Dulbecco's medium (IMDM) containing 10 % human serum albumin.

Inclusion Criteria: patients scheduled for breast cancer surgery Exclusion Criteria: compromised immune function (such as infection with the human immunodeficiency virus, immunodeficiency, or treatment with corticosteroids, immunosuppressive drugs, or chemotherapy) ASA > III age> 70 years old. patients refusal to the procedure. Infection of the skin at or near site of needle puncture. Coagulopathy . Drug hypersensitivity or allergy to the studied drugs. Central or peripheral neuropthy . Pre-operative opoid consumption ( within 24 hours preoperative ) Anomalies of the vertebral column .