CD8 T cells expressing NK associated receptors are increased in melanoma patients and display an effector phenotype

Abstract

CD8+ T cells can express NK-associated receptors (NKRs) that may regulate their cytolytic function. We have characterized the expression of several NKRs on peripheral blood CD8+ T cells from melanoma patients and compared them to age-matched healthy donors. The analysis performed includes HLA class I specific receptors (KIRs, LILRB1 and CD94/NKG2) and other NK receptors like CD57, CD56 and CD16. Melanoma patients showed a higher variability in the expression of NKRs on circulating CD8+ T cells than age-matched healthy donors. NKR expression on CD8+ T cells from melanoma patients showed a significant increase of KIR2DL2/L3/S2 (mAb gl183), CD244, CD57, CD56 and CD16. We have also found an increase of CD8+ CD28- CD27- T cells in melanoma patients. This subset represents terminally differentiated effector cells expressing CD244 and high levels of perforin. The expression of NKRs was also mainly restricted to this T cell subset. Altogether, circulating CD8+ T cells from melanoma patients display a distinct phenotype characterized by downregulation of costimulatory molecules and higher expression of NKRs. We suggest that the increased expression of NKRs on T cells may contribute to the final outcome of the immune response against melanoma both stimulating or inhibiting activation and differentiation to effector cells. Blocking inhibitory receptor function and enhancing activating receptors may represent new strategies with therapeutic potential against melanoma.

Natural Killer Receptors on CD8 T Cells and Natural Killer Cells from Different HLA-C Phenotypes in Melanoma Patients

“…When the study of NKRs on CD8 T cells was made according to the CD28 coexpression, it could be confirmed that the expression of NKRs, as previously reported (4,15), was more frequent on CD8 + CD28 À T cells than on CD8 + CD28 + T cells, both in patients and in controls.…”

“…These changes observed in the CD8 + T-cell population seem to be associated with a favorable prognosis, because they were not detected in lymph node metastatic melanoma patients, where the number of CD8 + CD28 À T cells was close to that of healthy individuals, suggesting that in advanced stages of the disease there is less availability for the activation of CD8 T cells (4). In this sense, our data are in agreement with those reported about the decrease of CD8 + DR + T cells in metastatic patients (12), but they are also able to show that the HLA-DR down-modulation in patients at this stage is specially restricted to the CD8 + CD28…”

A critical role for DAP10 and DAP12 in CD8+ T cell–mediated tissue damage in large granular lymphocyte leukemia

“…One of the major changes that occurs after chronic T-cell activation and cancerous conditions is the down-regulation of CD28 and expansion of CD8 ϩ CD28 null T cells. 26,[32][33][34][35][36] Consistent with previous findings, CD8 ϩ CD28 null T cells were dramatically overrepresented in the peripheral blood of LGLL patients compared with healthy donors, as shown in Figure 4A,B. The absolute number of CD8 ϩ CD28 null T cells present in the blood was greater in LGLL patients compared with healthy donors and nearly all of the patients' CD8 ϩ T cells lacked CD28 expression.…”

Detection of KIR3DS1 on the Cell Surface of Peripheral Blood NK Cells Facilitates Identification of a Novel Null Allele and Assessment of KIR3DS1 Expression during HIV-1 Infection

“…ϩ TCR␥␦ ϩ T cells (44), EBV-selected synovial TCR␣␤ ϩ T cell clones derived from rheumatoid arthritis patients (45), and expanded CD8 ϩ CD28 null T cells in melanoma patients (46). In addition, KIR2DS2 has been shown to be expressed by the CD4 ϩ CD28 null T cells that expand in some patients with rheumatoid arthritis (47).…”