T lymphocyte chemotactic chemokines in acute myelogenous leukemia (AML): local release by native human AML blasts and systemic levels of CXCL10 (IP-10), CCL5 (RANTES) and CCL17 (TARC)

Abstract

T cell targeting immunotherapy is now considered in acute myelogenous leukemia (AML), and local recruitment of antileukemic T cells to the AML microcompartment will then be essential. This process is probably influenced by both intravascular as well as extravascular levels of T cell chemotactic chemokines. We observed that native human AML cells usually showed constitutive secretion of the chemotactic chemokines CXCL10 and CCL5, whereas CCL17 was only released for a subset of patients and at relatively low levels. Coculture of AML cells with nonleukemic stromal cells (i.e., fibroblasts, osteoblasts) increased CXCL10 and CCL17 levels whereas CCL5 levels were not altered. However, a wide variation between patients in both CXCL10 and CCL5 levels persisted even in the presence of the stromal cells. Neutralization of CXCL10 and CCL5 inhibited T cell migration in the presence of native human AML cells. Furthermore, serum CCL17 and CXCL10 levels varied between AML patients and were determined by disease status (both chemokines) as well as patient age, chemotherapy and complicating infections (only CCL17). Thus, extravascular as well as intravascular levels of T cell chemotactic chemokines show a considerable variation between patients that may be important for T cell recruitment and the effects of antileukemic T cell reactivity in local AML compartments.