Impaired natural killer cell lysis in breast cancer patients with high levels of psychological stress is associated with altered expression of killer immunoglobin-like receptors.

Full Abstract

BACKGROUND:
We previously reported that cancer-related psychological stress is associated with reduced natural killer (NK) cell lysis. We hypothesized that reduced NK cell cytotoxicity in patients with increased levels of stress would correlate with alterations in the expression of inhibitory NK cell receptors (killer immunoglobulin-like receptors, or KIRs). The specific aim of this study was to examine KIR expression in patients with high or low levels of psychologic stress and correlate alterations in KIR expression with NK cell function.

MATERIALS AND METHODS:
Two hundred twenty-seven patients underwent baseline evaluation of cancer-related psychological stress and were randomized to psychosocial intervention versus observation. From this population, two groups were defined based on pretreatment measurements of NK lytic activity, stress levels, and the availability of cryopreserved peripheral blood mononuclear cells (PBMC). Group I (n=9) had low stress by the Impact of Events Scale (IES), and high NK cell lysis at the 50:1 effector:
target ratio (NK(50)=52-89%). Group II (n=8) had high stress and low NK(50) (27-52%). Lymphokine activated killer (LAK) activity, antibody dependent cellular cytotoxicity (ADCC), and expression of cytokine receptors, adhesion molecules, and killer immunoglobulin-like receptors (KIRs) were assessed in PBMC.

RESULTS:
Incubation of PBMC with NK-stimulatory cytokines (IL-2, IL-12, or IL-15) led to significant increases in cytotoxic activity regardless of IES/NK(50) scores. There were no significant group differences in NK cell surface expression of the IL-2 receptor components CD25 and CD122, antibody-dependent lysis of HER2/neu-positive SKBr3 cells treated with an anti-HER2/neu monoclonal antibody, expression of adhesion molecules (CD2, CD11a, CD18) and markers of activation (CD69), or expression of the KIRs CD158a, NKG2a, NKB1, and CD161. However, levels of CD158b were significantly higher in Group I after incubation in media alone or with IL-2, and CD94 expression was significantly lower in Group I after incubation with IL-2.

CONCLUSIONS:
In this study of a small subset of breast cancer patients chosen from a previous clinical trial of psychosocial intervention for breast cancer, impaired NK lysis in breast cancer patients with high levels of psychological stress was associated with alterations in surface expression of killer immunoglobulin-like receptors. However, immune effectors retained the ability to lyse antibody-coated targets and to initiate lymphokine-activated killer activity, irrespective of stress levels or baseline NK(50).

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Author information

Author/s: Varker, Kimberly A (KA); Terrell, Catherine E (CE); Welt, Marilyn (M); Suleiman, Samer (S); Thornton, Lisa (L); Andersen, Barbara L (BL); Carson, William E (WE);

Affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.

Grants: 5 T32 CA009338-27 (Agency:NCI NIH HHS) ; K24 CA093670-01A1 (Agency:NCI NIH HHS) ; K24 CA93670 (Agency:NCI NIH HHS) ; M01 RR000034-390574 (Agency:NCRR NIH HHS) ; M01 RR000034-476242 (Agency:NCRR NIH HHS) ; M01-RR0034 (Agency:NCRR NIH HHS) ; P01 CA095426-01A19002 (Agency:NCI NIH HHS) ; P01 CA95426 (Agency:NCI NIH HHS) ; P30 CA016058-289023 (Agency:NCI NIH HHS) ; R01 CA092704-06 (Agency:NCI NIH HHS) ; R01 CA092704-10 (Agency:NCI NIH HHS) ; R01 MH051487-04 (Agency:NIMH NIH HHS) ; R01 MH051487-05 (Agency:NIMH NIH HHS) ; R01 MH51487 (Agency:NIMH NIH HHS) ; R0192704 (Agency:PHS HHS) ; T32 CA009338-27 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: The Journal of surgical research (J Surg Res), published in United States. (Language: eng)

Reference: 2007-May; vol 139 (issue 1) : pp 36-44

Dates: Created 2007/04/02; Completed 2007/05/17; Revised 2008/11/21;

PMID: 17292412, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Aged
Antibody-Dependent Cell Cytotoxicity
Breast Neoplasms - immunology
Cytotoxicity, Immunologic
Female
Humans
Killer Cells, Natural - immunology

Middle Aged
NK Cell Lectin-Like Receptor Subfamily D - analysis
Receptors, Immunologic - analysis
Receptors, KIR
Receptors, KIR2DL1
Receptors, KIR2DL3
Receptors, KIR3DL1
Stress, Psychological - immunology

Associated Chemicals: KLRD1 protein, human (0) ; NK Cell Lectin-Like Receptor Subfamily D (0) ; Receptors, Immunologic (0) ; Receptors, KIR (0) ; Receptors, KIR2DL1 (0) ; Receptors, KIR2DL3 (0) ; Receptors, KIR3DL1 (0)

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