Sustained treatment‐free remission in chronic myeloid leukaemia is associated with an increased frequency of innate CD8(+) T‐cells

Abstract

Summary Immunological mechanisms of treatment‐free remission (TFR) in chronic myeloid leukaemia (CML) are poorly defined and, to date, no correlation between successful TFR and CD8(+) T‐cell subsets has been found. We analysed a new identified human subset of CD8(+) T‐cells, namely innate CD8(+) T‐cells, in CML patients with TFR ≥ 2 years. We demonstrated a dramatic increase of functionally active innate CD8(+) T‐cells in these patients as compared to control subjects and patients in remission under tyrosine kinase inhibitors. Moreover, we found a positive correlation between frequencies of innate CD8(+) T‐cells and natural killer cells, possibly representing a new innate biomarker profile of successful TFR.

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when and for whom?

“…• Other investigational studies have associated a higher percentage of innate T cells 37 or NK cells 38 with a better chance of TFR, suggesting that an immune surveillance mechanism is involved in maintaining molecular response.…”

“…A number of studies have evaluated T-cell and particularly NK-cell populations in patients in TFR, but none has been convincing and further studies are needed. 37,38 It is conceivable that residual clonogenic cells remain in a relatively quiescent state which may take years to manifest clinically, perhaps because of an eventual failure of immune control. With few exceptions, we do not know the interval between the original acquisition of the BCR-ABL1 mutation and the development of clinically apparent CML.…”

Current Strategies and Future Directions to Achieve Deep Molecular Response and Treatment-Free Remission in Chronic Myeloid Leukemia

“…The EURO-SKI also identified the importance of NK cells in maintaining remission after imatinib discontinuation in CML patients, suggesting an association between an increase in MRFS and a higher proportion of NK cells, which were mature and secreted TNF-α/interferon (IFN)-γ cytokine in non-relapsing patients (36). A significant positive correlation between the frequencies of innate CD8(+) T-cells and NK cells was identified in CML patients with TFR for ≥2 years after TKI discontinuation, which is suggestive of a link between these lymphocyte populations and may represent a novel innate biomarker of successful TFR (37).…”

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

“…A more general target are tyrosine kinases, which propagate many signaling pathways, and tyrosine kinase inhibitors (TKIs) are used in the clinic for various malignancies, such as chronic myeloid leukemia. Immunological control after the cessation of therapy with TKIs is associated with recovery of function in T VM cells that are exquisitely sensitive to age‐related chronic inflammation 137 . Indeed, pretreatment with a TKI, called ibrutinib, has improved T cell activation and outcomes of CAR T cell therapy in patients with chronic lymphocytic leukemia 138 .…”