Expression of co‐stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission

Abstract

Summary. Many solid tumours have been shown to lack expression of either of the immune co-stimulatory molecules CD80 (B7AE1) or CD86 (B7AE2), which is thought to be one of the ways in which tumours may escape immune recognition. We have examined the surface expression of CD80, CD86, human leucocyte antigen (HLA) class I and II, CD11a, CD54, and CD58 on the blast cells from patients with acute myeloid leukaemia (AML) at presentation. CD80 was only rarely expressed on AML blasts and, in those leukaemic cells expressing CD80, the level of expression was low. In contrast, expression of CD86 was detected on the AML blasts in more than half of the samples tested and, in some cases, the level of expression was equivalent to that of mature monocytes and activated B lymphocytes. The percentage of leukaemic blasts expressing CD86 was higher in the M4 and M5 French-American-British (FAB) types, and expression of CD11a and HLA class II was higher in the M4 FAB type. There was no difference in expression of CD80, CD54, CD58, or HLA Class I between different FAB subgroups. There was no significant difference in duration of first remission with expression of CD80, CD86, CD11a, CD54 or HLA class II. However, when expression of CD80 and CD86 were considered together, a significantly longer duration of remission was found. We suggest that these molecules may play a role in immunosurveillance, resulting in prolonged remission in some patients treated for AML.

T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia

“…The minimally differentiated KG1a cell line used in this model system does not express costimulatory molecules CD80/CD86, much like undifferentiated primary AML patient samples. 48 The antileukemic effect observed in our studies is comparable with what is often seen in xenogeneic models of acute leukemia void of tumor-derived costimulation, using either single or multiple infusions of CAR T cells. 9,49 The in vivo potency of our CD123 CAR T cells may be further augmented by using a less differentiated memory T-cell subset or by altering several features of the CAR including scFv affinity, linker length, and intracellular costimulatory domain (s), all of which have been shown to play key roles in CAR T-cell potency.…”

CTLA-4 Is Expressed by Activated Mouse NK Cells and Inhibits NK Cell IFN-γ Production in Response to Mature Dendritic Cells

“…Its function in human NK cells remains to be investigated. B7-1 is endogenously expressed only by certain tumor cells (48)(49)(50), but it is often highly expressed by activated APCs. In this context, our data demonstrate that CD28/CTLA-4 differentially modulate IFN-g release by NK cells in response to mDCs.…”

CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy

“…Moreover, the previously described low level of expression of costimulatory molecules on the surface of leukemic blasts may also facilitate tumor escape from immune system action. 14 However, it has been reported that vaccination strategies using leukemia-associated antigens, such as WT1 or PR1, may be associated with the development of specific autologous cytotoxic T cells and with clinical responses, suggesting that the autologous immune response is important in the control of leukemic proliferation. 15 We found that AML patients with the CTLA4 CT60 AA genotype have a higher relapse incidence after obtaining a first complete remission with standard chemotherapy, leading to worse OS.…”