Evaluation of PD1 / PDL1 Expression on Blood Cells & Tumor Tissue, Their Role as a Prognostic Target in NSCLC Patients

NCT ID: NCT02758314

Last Updated: 2016-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-03-31

Study Completion Date

2018-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Small Cell Lung Cancer

Keywords

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PD-1 PD-L1 NSCLC

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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 Cancerología (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.

Evaluation of PD-1/PDL-1 expression.

Intervention Type 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

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 Cancerología (INCan)

Evaluation of PD-1/PDL-1 expression.

Intervention Type 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

Interventions

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Evaluation of PD-1/PDL-1 expression.

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Patients who have understood and signed the informed consent.
2. Diagnosis of lung cancer, histologically or cytologically documented (stage IIIA / B or IV) non-small cell adenocarcinoma, which had not received radiotherapy and / or chemotherapy prior to the first sample.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and evidence of measurable disease.


1. Informed consent in writing (signed) to participate in the study.
2. No diagnosis of oncological disease.
3. Subjects without symptoms of any respiratory illness in the two weeks prior to sampling.

Exclusion Criteria

1. Subjects with Non-small cell lung cancer with a different histological type to adenocarcinoma.
2. Subjects with acute inflammation and uncontrolled infections.


1\. Any unstable systemic disease (including active or metabolic infection, congestive heart failure, liver disease, kidney).
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Instituto Nacional de Cancerologia de Mexico

OTHER

Sponsor Role lead

Responsible Party

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Oscar Gerardo Arrieta Rodríguez MD

Director and Head of Functional Unit of Thoracic Oncology and Personalized Medicine Laboratory. SNI III

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Oscar Gerardo MD Arrieta Rodriguez, Oncology

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Cancerologia, Mexico

Locations

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Instituto National de Cancerologia

México, State of Mexico, Mexico

Site Status

Countries

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Mexico

Central Contacts

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Oscar Gerardo MD Arrieta Rodriguez, Oncology

Role: CONTACT

Phone: 01 52 556280400

Email: [email protected], [email protected]

GRACIELA Cruz, Biochemistry

Role: CONTACT

Phone: 015556280400

Email: [email protected]

Facility Contacts

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Oscar Gerardo MD Arrieta, Oncology

Role: primary

Graciela Cruz, Biochemistry

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 24048123 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15771580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26069281 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27039716 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29254220 (View on PubMed)

Other Identifiers

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INCAN/CI/498/13

Identifier Type: -

Identifier Source: org_study_id