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Several reports have examined Programmed Death 1 (PD-1) expression on tumor-infiltrating T-cells, and its correlation with prognosis has been discussed. However, Programmed Death 1 (PD1)/Programmed Death Ligand 1 (PDL1) expression on the peripheral blood T-cells of cancer patients, particularly in those with lung cancer, has not been sufficiently studied. The purpose of this study is evaluate the expression of PD1 and PDL1 in subpopulations of peripheral blood and tumor cells patients with lung cancer non-small cell (NSCLC), associating with clinicopathological features of the patients studied.
This is a prospective cohort study including patients with NSCLC stages IIIA, IIIB and IV lung cancer clinic of the National Cancer Institute (INCAN)
Clinical samples. Prior and informed consent before receiving any treatment, sample be obtained 15 ml peripheral blood of each subject included in the study (patients and controls). mononuclear peripheral blood cells (PBMC) from different groups of subjects separated by centrifugation gradient (Polymorphprep, Accurate Chemical) are used. The cells are resuspended in dimethylsulfoxide (DMSO) and 10% fetal bovine serum (FBS) to 90% at a concentration of 1 million cells per ml and kept in liquid nitrogen until use.
Evaluation of PD-1, PD-L1 by flow cytometry. The following monoclonal antibodies directed against cell surface antigens of human are used: anti-PD-1, anti-PD-L1, anti-PD-L2, anti- cluster of differentiation (CD) 3, anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD56, anti-CD19, anti-CD20.
Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC). Lung biopsy is obtained paraffin blocks, and are processed by IHC technique for antitumor expression of PD1 / PDL1.V PD-L1 immunostaining was classified into two groups according to intensity and extent: (a) negative, when no staining or positive staining was detected in <5% of the cells; and (b) positive, when membranous staining was present in P5% of the cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cases / NSCLC patients | Evaluation of PD-1/PDL-1 expression. Evaluate the expression of PD-1 / PD-L1 on T-cell subpopulations (CD3 + (CD4 +, CD8 +), B cells (CD19 + CD20 +), natural killer (NK) cells (CD16 + CD56 +) NK T-cells (CD3 + CD16 + CD56 + ) peripheral blood samples in 150 NSCLC, free treatment by flow cytometry. Evaluate the expression of PD-1 / PD-L1 in tumor tissue obtained by biopsy of patients with NSCLC by immunohistochemistry. The patients for the enrollment have to be diagnosed with advanced Non-Small Cell Lung Adenocarcinoma (clinical stages IIIA, IIIB and IV), treated at the Instituto Nacional de CancerologÃa (INCan) who had not received radiotherapy and / or chemotherapy prior to obtaining samples to analyze. ECOG performance status 0-2 and present evidence of measurable disease. |
| |
| Control / Healthy subjects | Evaluation of PD-1/PDL-1 expression. Evaluate the expression of PD-1 / PD-L1 on T-cell subpopulations (CD3 + (CD4 +, CD8 +), B cells (CD19 + CD20 +), natural killer (NK) cells (CD16 + CD56 +) NK T-cells (CD3 + CD16 + CD56 + ) peripheral blood samples in 50 samples, by flow cytometry. Healthy subjects blood cells will be obtained from the blood bank at the Instituto Nacional de CancerologÃa (INCan) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evaluation of PD-1/PDL-1 expression. | Other | Evaluate the expression of PD-1 / PD-L1 on T-cell subpopulations of peripheral blood by flow cytometry and in tumor tissue by immunohistochemistry in NSCLC, free treatment and healthy subjects |
| Measure | Description | Time Frame |
|---|---|---|
| Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC) | Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC). Lung biopsy is obtained paraffin blocks, and are processed by IHC technique for antitumor expression of PD1 / PDL1.V PD-L1 immunostaining was classified into two groups according to intensity and extent: (a) negative, when no staining or positive staining was detected in <5% of the cells; and (b) positive, when membranous staining was present in P5% of the cells. | Baseline evaluation |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of PD-1, PD-L1 by flow cytometry. | Evaluation of PD-1, PD-L1 by flow cytometry. The following monoclonal antibodies directed against cell surface antigens of human are used: anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation 3 (CD3), anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD56, anti-CD19, anti-CD20. | Baseline evaluation |
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Inclusion Criteria patient :
Exclusion Criteria patient:
Inclusion Criteria healthy subjects :
Exclusion criteria healthy volunteers.
1. Any unstable systemic disease (including active or metabolic infection, congestive heart failure, liver disease, kidney).
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It will include patients diagnosed with advanced non-small cell lung adenocarcinoma (clinical stages IIIA, IIIB and IV) treated at the Instituto Nacional de CancerologÃa (INCan).
Subjects without previous radiotherapy and / or chemotherapy (prior sampling).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Oscar Gerardo MD Arrieta Rodriguez, Oncology | Contact | 01 52 556280400 | 71101 | ogarrieta@gmail.com, ogartsrr@yahoo.com.mx |
| GRACIELA Cruz, Biochemistry | Contact | 015556280400 | 71101 | gracielacr@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Oscar Gerardo MD Arrieta Rodriguez, Oncology | Instituto Nacional de Cancerologia, Mexico | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto National de Cancerologia | México | State of Mexico | 14080 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24048123 | Background | Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013 Oct;14(10):1014-22. doi: 10.1038/ni.2703. | |
| 15771580 | Background | Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515-48. doi: 10.1146/annurev.immunol.23.021704.115611. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jan 2, 2019 | |
| Reset | Apr 4, 2019 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jan 2, 2019 | Apr 4, 2019 |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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Whole blood cells, serum and plasma, tumor tissue
| 26069281 | Background | Pennock GK, Chow LQ. The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment. Oncologist. 2015 Jul;20(7):812-22. doi: 10.1634/theoncologist.2014-0422. Epub 2015 Jun 11. |
| 27039716 | Background | Su M, Huang CX, Dai AP. Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer. Asian Pac J Cancer Prev. 2016;17(3):905-10. doi: 10.7314/apjcp.2016.17.3.905. |
| 29254220 | Derived | Arrieta O, Montes-Servin E, Hernandez-Martinez JM, Cardona AF, Casas-Ruiz E, Crispin JC, Motola D, Flores-Estrada D, Barrera L. Expression of PD-1/PD-L1 and PD-L2 in peripheral T-cells from non-small cell lung cancer patients. Oncotarget. 2017 Oct 24;8(60):101994-102005. doi: 10.18632/oncotarget.22025. eCollection 2017 Nov 24. |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |