Innate T Cells and TKI Discontinuation

Study Overview
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Brief Summary
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After more than a decade of treating chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI), the discontinuation of treatment represents the expected new revolution. The investigators has recently discovered a new innate CD8+ T population in healthy subjects, the Eomes+ KIR+ CD8+ T population, with anti-tumor properties. Remarkably, these cells are numerically and functionally deficient in patients at diagnosis and then restored in patients in major molecular remission (MMR) on TKI. Our work performed in a retrospective pilot study interestingly shows a very significant increase in the proportion of CD8+ Eomes+ KIR+ T cells within total T cells in patients with prolonged success in stopping their ITK (≥ 2 years).Thus, the investigators postulate that CD8+ Eomes+ KIR+ T cells are a predictive signature of TKI arrest success in CML. The investigators will rely on a prospective translational study of this cell contingent during treatment cessation.

Detailed Description
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To perform this research, the investigators have started a prospective translational study to collect samples in CML patients with successful versus patients who have failed TKI therapy discontinuation. The investigators plan to study functional and phenotypic characteristics of innate T cells. The investigators also plan to evaluate in vitro whether immune check points inhibitors could help to restore the innate T lymphocytes population.

Official Title
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Innate T-cells as a Biomarker of Successful TKI Arrest in Chronic Myeloid Leukemia

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Other: Characteristics of innate T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Diagnosis of CML-PC according to the criteria of the European Leukemia Net (Baccarani et al, 2013) Patients treated with TKI for at least 3 years (imatinib, nilotinib, dasatinib, bosutinib, ponatinib) Patients meeting the criteria of the French STIM study: deep molecular response of MR4.5 type (threshold of 0.0032%) or MR5 type (threshold of 0.001%) for at least 2 years, Free subject, without guardianship or curatorship or subordination Patients benefiting from a Social Security system or benefiting from it through a third party Exclusion Criteria: Refusal to participate in the research Patients not benefiting from a Social Security scheme or not benefiting from it through a third party Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies Patient having stopped treatment for another reason than: deep molecular response of MR4.5 (threshold of 0.0032%) or MR5 (threshold of 0.001%) for at least 2 years Translated with www.DeepL.com/Translator (free version)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Characteristics of innate T cells|functional and phenotypic characteristics of innate T cells|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the quantitative characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment | Proportion of the CD8+ Eomes+ KIR+ T cells among CD8+ T cells between patients in failure versus those in success after discontinuation of TKI treatment | Day 0 (day of discontinuing treatment) | 
| Compare phenotypic characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment | Phenotypic markers expression : CD49d, CD57, CD45RA et CCR7, CD25 et HLA-DR among total CD8+ T cells | Day 0 (day of discontinuing treatment) | 
| Compare the functionnality of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment | Functionality of LT CD8+ Eome+ KIR+ : expression of perforin and IFNgamma | Day 0 (day of discontinuing treatment) |