CD62L T-cell expression linked to TKI therapy response
medwireNews: Chronic myeloid leukemia (CML) patients with high CD62L T-cell expression and low soluble (s)CD62L plasma levels at diagnosis have the best chance of achieving a deep molecular response to first-line therapy with tyrosine kinase inhibitors (TKIs), study findings indicate.
The researchers, led by Dominik Wolf (University Clinic Bonn, Germany), used comprehensive flow cytometry-based immunomonitoring to prospectively study 52 nilotinib-naïve patients with early chronic-phase CML who were participating in the ENEST1st clinical trial.
They found that, at diagnosis, a median of 5.7% of CD4+ T cells and 2.8% of CD8+ T cells expressed CD62L. After 6 months of treatment with nilotinib, these values had risen to around 70% and 40%, respectively, and were similar to the levels observed in healthy individuals.
The level of CD62L expression inversely correlated with Sokal score, spleen size, leukocyte and peripheral-blood blast counts, and BCR–ABL1 copy numbers during treatment.
And when the researchers split the group into those with high (above median) versus low CD62L expression, they found that significantly more patients in the CD62L-high group achieved a deep molecular response at 18 months, compared with those in the CD62L-low group, at 62.5% versus 13.0%.
Wolf and team note that “CD62L can be shed when T cells become activated, leading to an increase of sCD62L.” In line with this, they found that the level of CD62L loss on T cells directly correlated with the extent of sCD62L elevation.
Specifically, sCD62L levels were high at diagnosis and decreased during nilotinib therapy as CD62L T-cell expression increased.
Alongside this finding, the researchers also observed increased tumor necrosis factor α-converting enzyme (TACE) activity in pretreatment CML plasma samples that significantly decreased during nilotinib treatment.
The researchers explain that this enzyme proteolytically cleaves membrane-bound CD62L, and they found that its activity inversely correlated with CD62L expression on CD4+ T cells and positively correlated with sCD62L plasma levels.
“Functionally, decreased CD62L may be a consequence of increased TACE-mediated CD62L cleavage and potentially impairs immune-cell function,” they remark in the Journal of Clinical Oncology.
The authors conclude that although their findings were validated in two independent cohorts, further validation is needed and should include later CML phases and other TKIs.
They add that “the mechanisms causing deregulated TACE activity and the role of TACE in T cell–mediated leukemia-specific immune surveillance in more aggressive and less TKI-sensitive [chronic-phase] CMLs have to be defined in future projects.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2017