Clinical trial NCT02758314: Evaluation of PD1 / PDL1 Expression on Blood Cells & Tumor Tissue, Their Role as a Prognostic Target in NSCLC Patients
Official title: Clinical Pathological Features Associated With the Expression of PD1 / PD-L1 in Subpopulations of Peripheral Blood and Tumor Tissue in Patients With Advanced Non-small Cell Lung Cancer, Their Role as Prognostic and Therapeutic Targets
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Non-Small Cell Lung Cancer
Keywords: PD-1
PD-L1
NSCLC
Lead sponsor: Instituto Nacional de Cancerologia de Mexico
Sponsor class: OTHER
First posted: 2016-05-02
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: It will include patients diagnosed with advanced non-small cell lung adenocarcinoma (clinical stages IIIA, IIIB and IV) treated at the Instituto Nacional de Cancerología (INCan).

Subjects without previous radiotherapy and / or chemotherapy (prior sampling).

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria patient :

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.

Exclusion Criteria patient:

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

Inclusion Criteria healthy subjects :

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 healthy volunteers.

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

Primary outcomes:
measure: Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC)
timeFrame: Baseline evaluation
Secondary outcomes:
measure: Evaluation of PD-1, PD-L1 by flow cytometry.
timeFrame: Baseline evaluation
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: Instituto National de Cancerologia
Study officials:
affiliation: Instituto Nacional de Cancerologia, Mexico
name: Oscar Gerardo MD Arrieta Rodriguez, Oncology
role: PRINCIPAL_INVESTIGATOR
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citation: 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.