Increased Expression of TIGIT/CD57 in Peripheral Blood/Bone Marrow NK Cells in Patients with Chronic Myeloid Leukemia

Area of Science:

• Immunology
• Hematology
• Cancer Biology

Background:

• The leukemia microenvironment suppresses natural killer (NK) cell antitumor activity in chronic myeloid leukemia (CML).
• TIGIT, CD57, and KLRG1 expression are linked to NK cell function, maturation, and antitumor capabilities.
• The specific expression patterns of these markers in CML patients' peripheral blood (PB) and bone marrow (BM) are not well understood.

Purpose of the Study:

• To investigate the expression characteristics of TIGIT, CD57, and KLRG1 on NK cells in the PB and BM of CML patients.
• To correlate these findings with NK cell function and patient response to treatment.

Main Methods:

• Multicolor flow cytometry was employed to analyze NK cell quantity and phenotype.
• Samples were collected from de novo CML (DN-CML) patients, CML patients achieving molecular response (MR-CML), and healthy individuals (HIs).
• Analysis focused on NK cells in both peripheral blood (PB) and bone marrow (BM).

Main Results:

• TIGIT expression was significantly increased on CD56+ and CD56dim NK cells in DN-CML PB compared to HIs; this returned to normal in MR-CML patients.
• CD57 expression levels were similar in PB and BM of DN-CML patients, but decreased on NK cells in HI BM compared to HI PB.
• CD56+ and CD56dim NK cells showed significantly increased CD57 expression in DN-CML BM compared to HI BM, correlating with senescence and maturity.

Conclusions:

• Elevated TIGIT on PB NK cells and increased CD57 on BM NK cells in DN-CML patients likely contribute to reduced NK cell antileukemia capacity and proliferation.
• Targeting TIGIT to reverse immune suppression in PB NK cells and targeting CD57 to enhance BM NK cell proliferation may be effective therapeutic strategies.
• These findings offer insights into modulating NK cell function for improved CML treatment.