TY - JOUR
T1 - CRTAM + NK cells endowed with suppressor properties arise in leukemic bone marrow
AU - Ramírez-Ramírez, Dalia
AU - Padilla-Castañeda, Sandra
AU - Galán-Enríquez, Carlos Samuel
AU - Vadillo, Eduardo
AU - Prieto-Chávez, Jessica Lakshmi
AU - Jiménez-Hernández, Elva
AU - Vilchis-Ordóñez, Armando
AU - Sandoval, Antonio
AU - Balandrán, Juan Carlos
AU - Pérez-Tapia, Sonia Mayra
AU - Ortiz-Navarrete, Vianney
AU - Pelayo, Rosana
N1 - Publisher Copyright:
©2019 Society for Leukocyte Biology
PY - 2019/5
Y1 - 2019/5
N2 - Due to their increasing rates of morbidity and mortality, childhood malignancies are considered a global health priority, with acute lymphoblastic leukemias (ALLs) showing the highest incidence worldwide. Control of malignant clone emergence and the subsequent normal-leukemic hematopoietic cell out-competition require antitumor monitoring mechanisms. Investigation of cancer surveillance innate cells may be critical to understand the mechanisms contributing in either disease progression or relapse, and to promote displacement of leukemic hematopoiesis by the normal counterpart. We report here that NK cell production is less and low hematopoietic progenitor numbers contribute to this defect. By investigating the expression of the activation molecule class I restricted T-cell associated molecule (CRTAM) along the hematopoietic lineage differentiation pathway, we have identified lymphoid precursor populations coexpressing CD34, CD56/CD3/CD19, and CRTAM as the earliest developmental stage where activation may take place in specialized niches that display the ligand nectin-like-2. Of note, bone marrow (BM) from patients with ALL revealed high contents of preactivated CD56 high NK cells expressing CRTAM and endowed with an exhaustion-like phenotype and the functional capability of producing IL-10 and TGF-β in vitro. Our findings suggest, for the first time, that the tumor microenvironment in ALL directly contribute to exhaustion of NK cell functions by the CRTAM/Necl-2 interaction, and that the potential regulatory role of exhausted-like NK cells may favor malignant progression at the expense of anti-tumor responses. Phenotypic and functional identity of this unique suppressor-like NK cell population within the leukemic BM would be of special interest for the pathobiology of ALL and development of targeting strategies.
AB - Due to their increasing rates of morbidity and mortality, childhood malignancies are considered a global health priority, with acute lymphoblastic leukemias (ALLs) showing the highest incidence worldwide. Control of malignant clone emergence and the subsequent normal-leukemic hematopoietic cell out-competition require antitumor monitoring mechanisms. Investigation of cancer surveillance innate cells may be critical to understand the mechanisms contributing in either disease progression or relapse, and to promote displacement of leukemic hematopoiesis by the normal counterpart. We report here that NK cell production is less and low hematopoietic progenitor numbers contribute to this defect. By investigating the expression of the activation molecule class I restricted T-cell associated molecule (CRTAM) along the hematopoietic lineage differentiation pathway, we have identified lymphoid precursor populations coexpressing CD34, CD56/CD3/CD19, and CRTAM as the earliest developmental stage where activation may take place in specialized niches that display the ligand nectin-like-2. Of note, bone marrow (BM) from patients with ALL revealed high contents of preactivated CD56 high NK cells expressing CRTAM and endowed with an exhaustion-like phenotype and the functional capability of producing IL-10 and TGF-β in vitro. Our findings suggest, for the first time, that the tumor microenvironment in ALL directly contribute to exhaustion of NK cell functions by the CRTAM/Necl-2 interaction, and that the potential regulatory role of exhausted-like NK cells may favor malignant progression at the expense of anti-tumor responses. Phenotypic and functional identity of this unique suppressor-like NK cell population within the leukemic BM would be of special interest for the pathobiology of ALL and development of targeting strategies.
KW - CRTAM
KW - NK suppressor cells
KW - acute lymphoblastic leukemia
KW - bone marrow
KW - exhausted-like NK cells
UR - http://www.scopus.com/inward/record.url?scp=85064601697&partnerID=8YFLogxK
U2 - 10.1002/JLB.MA0618-231R
DO - 10.1002/JLB.MA0618-231R
M3 - Artículo
C2 - 30791148
AN - SCOPUS:85064601697
SN - 0741-5400
VL - 105
SP - 999
EP - 1013
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -