scholarly journals The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans

2009 ◽  
Vol 206 (7) ◽  
pp. 1495-1503 ◽  
Author(s):  
Cameron S. Brandt ◽  
Myriam Baratin ◽  
Eugene C. Yi ◽  
Jacob Kennedy ◽  
Zeren Gao ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Tumor ◽  
Cell Surface Molecule ◽  
B7 Family

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.

Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell–mediated cytotoxicity

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3304-3310 ◽  
Author(s):  
Theresa A. Caragine ◽  
Masaki Imai ◽  
Alan B. Frey ◽  
Stephen Tomlinson
Keyword(s):  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Nk Cell ◽  
Human Tumor ◽  
Mammary Adenocarcinoma ◽  
Tumor Cell Lines ◽  
Human Tumor Cell

Abstract Crry is a rodent membrane–bound inhibitor of complement activation and is a structural and functional analog of the human complement inhibitors decay-accelerating factor and membrane cofactor protein. We found previously that expression of rat Crry on a human tumor cell line enhances tumorigenicity in nude rats. In this study, we investigated the effect that rat Crry expressed on tumor cells has on rat cell–mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The expression of rat Crry on the surface of different human tumor cell lines inhibited ADCC mediated by rat natural killer (NK) cells. C3 opsonization is known to enhance NK cell–mediated cytolysis, and a potential mechanism for Crry-mediated inhibition of NK cell lysis is through Crry modulation of C3 deposition on target cells. However, the transfection of tumor cell lines with Crry enhanced their resistance to NK cell–mediated lysis in the absence of exogenous complement. The resistance of Crry-expressing tumor cells to NK cell–mediated ADCC could be reversed by treatment with anti–Crry F(ab)2. In addition, anti–Crry F(ab)2 enhanced the susceptibility of 13762 rat mammary adenocarcinoma cells (that endogenously express Crry) to ADCC mediated by allogeneic rat NK cells in the absence of added complement. We found no evidence that rat NK cells were a source of complement for target cell deposition during the in vitro cytolysis assay. These data suggest a novel function for rat Crry in tumor immune surveillance that may be unrelated to complement inhibition.

scholarly journals Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Endocrines ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 121-132
Author(s):  
Erik D. Hanson ◽  
Lauren C. Bates ◽  
Kaileigh Moertl ◽  
Elizabeth S. Evans
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Cancer Survivors ◽  
Nk Cells ◽  
Natural Killer ◽  
Acute Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Current Evidence ◽  
Cell Mobilization

Natural killer (NK) cells from the innate immune system are integral to overall immunity and also in managing the tumor burden during cancer. Breast (BCa) and prostate cancer (PCa) are the most common tumors in U.S. adults. Both BCa and PCa are frequently treated with hormone suppression therapies that are associated with numerous adverse effects including direct effects on the immune system. Regular exercise is recommended for cancer survivors to reduce side effects and improve quality of life. Acute exercise is a potent stimulus for NK cells in healthy individuals with current evidence indicating that NK mobilization in individuals with BCa and PCa is comparable. NK cell mobilization results from elevations in shear stress and catecholamine levels. Despite a normal NK cell response to exercise, increases in epinephrine are attenuated in BCa and PCa. The significance of this potential discrepancy still needs to be determined. However, alterations in adrenal hormone signaling are hypothesized to be due to chronic stress during cancer treatment. Additional compensatory factors induced by exercise are reviewed along with recommendations on standardized approaches to be used in exercise immunology studies involving oncology populations.

scholarly journals 799 Neoantigen-cytokine-chemokine multifunctional natural killer cell engager for immunotherapy of solid tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A834-A834
Author(s):  
Xue Yao ◽  
Sandro Matosevic
Keyword(s):  
Tumor Microenvironment ◽  
Cell Therapy ◽  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Nk Cell Therapy

BackgroundThe effectiveness of natural killer (NK) cell-based immunotherapy against solid tumors is limited by the lack of specific antigens and the immunosuppressive tumor microenvironment (TME). Glioblastoma multiforme (GBM) is one such heavily immunosuppressive tumor that has been particularly hard to target and remains without a viable treatment. The development of novel approaches to enhance the efficacy of NK cells against GBM is urgently needed. NK cell engagers (NKCE) have been developed to enhance the efficacy of NK cell therapy.MethodsTo improve the clinical efficacy of NK cell therapy, we are developing a new generation of multi-specific killer engagers, which consists of a neoantigen-targeting moiety, together with cytokine and chemokine-producing domains. Neoantigens are new antigens formed specifically in tumor cells due to genome mutations, making them highly specific tools to target tumor cells. Our engager has been designed to target Wilms' tumor-1 (WT-1), a highly specific antigen overexpressed in GBM among other solid tumors. This is done through the generation of an scFv specific targeting the complex of WT-1126-134/HLA-A*02:01 on the surface of GBM. On the NK cell side, the engager is designed to target the activating receptor NKp46. Incorporation of the cytokine IL-15 within the engager supports the maturation, persistence, and expansion of NK cells in vivo while favoring their proliferation and survival in the tumor microenvironment. Additionally, our data indicated that the chemokine CXCL10 plays an important role in the infiltration of NK cells into GBM, however, GBM tumors produce low levels of this chemokine. Incorporation of a CXCL10-producing function into our engager supports intratumoral NK cell trafficking by promoting, through their synthetic production, increased levels of CXCL10 locally in the tumor microenvironment.ResultsCollectively, this has resulted in a novel multifunctional NK cell engager, combining neoantigen-cytokine-chemokine elements fused to an activating domain-specific to NK cells, and we have investigated its ability to support and enhance NK cell-mediated cytotoxicity against solid tumors in vitro and in vivo against patient-derived GBM models. The multi-specific engager shows both high tumor specificity, as well as the ability to overcome NK cell dysfunction encountered in the GBM TME.ConclusionsWe hypothesize that taking advantage of our multi-functional engager, NK cells will exhibit superior ex vivo expansion, infiltration, and antitumor activity in the treatment of GBM and other solid tumors.

scholarly journals Bortezomib Augments Natural Killer Cell Targeting of Stem-Like Tumor Cells

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 85 ◽  
Author(s):  
Jesus Luna ◽  
Steven Grossenbacher ◽  
Ian Sturgill ◽  
Erik Ames ◽  
Sean Judge ◽  
...  
Keyword(s):  
Stem Cell ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Killer Cell ◽  
Human Tumor ◽  
Growth Delay ◽  
Cell Targeting ◽  
Immunodeficient Mice

Tumor cells harboring stem-like/cancer stem cell (CSC) properties have been identified and isolated from numerous hematological and solid malignancies. These stem-like tumor cells can persist following conventional cytoreductive therapies, such as chemotherapy and radiotherapy, thereby repopulating the tumor and seeding relapse and/or metastasis. We have previously shown that natural killer (NK) cells preferentially target stem-like tumor cells via non- major histocompatibility complex (MHC) restricted mechanisms. Here, we demonstrated that the proteasome inhibitor, bortezomib, augments NK cell targeting of stem cell-like tumor cells against multiple solid human tumor-derived cancer lines and primary tissue samples. Mechanistically, this was mediated by the upregulation of cell surface NK ligands MHC class I chain-related protein A and B (MICA and MICB) on aldehyde dehydrogenases (ALDH)-positive CSCs. The increased expression of MICA and MICB on CSC targets thereby enhanced NK cell mediated killing in vitro and ex vivo from both human primary tumor and patient-derived xenograft samples. In vivo, the combination of bortezomib and allogeneic NK cell adoptive transfer in immunodeficient mice led to increased elimination of CSCs as well as tumor growth delay of orthotopic glioblastoma tumors. Taken together, our data support the combination bortezomib and NK transfer as a strategy for both CSC targeting and potentially improved outcomes in clinical cancer patients.

Hemostatic Factors Contribute to Tumor Cell Metastatic Potential by a Mechanism Linked to Natural Killer Cell Function.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 690-690 ◽  
Author(s):  
Joseph S. Palumbo ◽  
Kathryn E. Talmage ◽  
Jessica V. Massari ◽  
Christine M. La Jeunesse ◽  
Matthew J. Flick ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Platelet Activation ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Metastatic Potential ◽  
Natural Killer Cell Function

Abstract A linkage between hemostatic system components and tumor cell metastatic potential has been well established, but the underlying mechanism(s) by which various circulating and cell-associated coagulation factors and platelets promote tumor cell dissemination remains to be fully defined. One potential mechanism by which tumor cell-associated microthrombi might enhance metastatic potential is by interfering with the cytolytic elimination of tumor cell emboli by natural killer (NK) cells. In order to explore this hypothesis, we studied tumor dissemination in mice lacking either fibrinogen or Gαq, a G protein critical for platelet activation. Comparative studies of experimental lung metastasis in control and Gαq−/− mice showed that loss of platelet activation resulted in a two-orders-of-magnitude decrease in pulmonary metastatic foci formed by either Lewis lung carcinoma or B16 melanoma. The difference in metastatic success was not the result of differences in tumor growth rate, as tumors transplanted into the dorsal subcutis of Gαq−/− and wildtype animals grew at similar rates. Rather, tumor cell fate analyses using radiolabeled tumor cells showed that the survival of tumor cells within the lung was significantly improved in mice that retained platelet activation function relative to Gαq−/− mice with a profound platelet activation defect. In order to examine the potential interplay between platelet activation and natural killer cell function, we compared pulmonary tumor cell survival in cohorts of control and Gαq−/− mice immuno-depleted of NK cells with an anti-asialo GM1 antibody. Remarkably, platelet function was no longer a determinant of metastatic potential in mice lacking NK cells. Given that fibrin(ogen) is also an established determinant of metastatic success we explored whether the influence of this key hemostatic factor on tumor cell dissemination was also mechanistically-coupled to natural killer cell function. We interbred fibrinogen-deficient mice with Gz-Ly49A transgenic mice known to have a constitutive deficit in NK cells. In those cohorts of mice with normal NK cells, we affirmed the earlier finding that fibrinogen deficiency resulted in a significant diminution in metastatic potential. However, consistent with our findings in mice with defective platelet activation, fibrinogen was found to no longer be a determinant of metastatic potential in mice lacking NK cells. These data establish another important link between innate immune surveillance and the hemostatic system. Further, it appears that at least one mechanism by which tumor cell-associated microthrombi increase metastatic potential is by restricting NK cell-mediated tumor cell elimination. Given that NK cell cytotoxicity requires direct contact with any target cell, one attractive model presently being explored is that tumor cell-associated platelets physically block NK cell access to tumor cell emboli.

scholarly journals The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2286-2294 ◽  
Author(s):  
Don M. Benson ◽  
Courtney E. Bakan ◽  
Anjali Mishra ◽  
Craig C. Hofmeister ◽  
Yvonne Efebera ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Response ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Immune Response ◽  
Cell Versus

Abstract T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti–PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1+ MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered.

scholarly journals Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Chaopin Yang ◽  
Yue Li ◽  
Yaozhang Yang ◽  
Zhiyi Chen
Keyword(s):  
Immune Function ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Therapeutic Potential ◽  
Tumor Therapy ◽  
Killer Cell ◽  
Oncolytic Viruses ◽  
Target Area

NK cells are lymphocytes with antitumor properties and can directly lyse tumor cells in a non-MHC-restricted manner. However, the tumor microenvironment affects the immune function of NK cells, which leads to immune evasion. This may be related to the pathogenesis of some diseases. Therefore, great efforts have been made to improve the immunotherapy effect of natural killer cells. NK cells from different sources can meet different clinical needs, in order to minimize the inhibition of NK cells and maximize the response potential of NK cells, for example, modification of NK cells can increase the number of NK cells in tumor target area, change the direction of NK cells, and improve their targeting ability to malignant cells. Checkpoint blocking is also a promising strategy for NK cells to kill tumor cells. Combination therapy is another strategy for improving antitumor ability, especially in combination with oncolytic viruses and nanomaterials. In this paper, the mechanisms affecting the activity of NK cells were reviewed, and the therapeutic potential of different basic NK cell strategies in tumor therapy was focused on. The main strategies for improving the immune function of NK cells were described, and some new strategies were proposed.

543 Natural killer cells restrict the growth of liver metastases in nude hosts

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A579-A579
Author(s):  
Alexandra Quackenbush ◽  
Pepper Schedin
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Liver Metastases ◽  
Nk Cells ◽  
Natural Killer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Nk Cell ◽  
Cell Depletion

BackgroundCancer patients with liver metastases have limited treatment options, especially as only 15–20% are eligible for curative-intent surgical resection.1 Unfortunately, liver metastases also seem to be poorly responsive to immune checkpoint inhibitors (ICI)].2 3 It could be that the unique immunological hallmarks of the liver, including resident macrophages and significant numbers of NK and NKT cells, create a tumor microenvironment that is best suited to alternative forms of immunotherapy that do not rely exclusively on ICI.MethodsWe investigated how the presence of T, natural killer (NK), and NKT cells impact overt liver metastases using a model in which tumor cells are delivered to the liver via intraportal injection to hosts that were either wiltype, nude, or nude with NK-depletion. NK cell depletion was achieved via administration of anti-asialo GM1 antibody 2 days before tumor cell injection and for the duration of the experiment until endpoint at 6 weeks post tumor cell injection, with NK cell depletion confirmed by flow cytometry. Tumors were assessed histologically.ResultsUsing the portal vein model in female nulliparous mice, overt liver metastasis incidence was about 30% across 2 different mammary tumor cell lines. The incidence rose to 80–100% when tumor cells were delivered to hosts in the post-wean window (referred to as involution hosts), mirroring increased breast cancer metastasis to the liver observed in postpartum breast cancer patients.4 Conversely, when tumor cells were delivered to nude hosts, either nulliparous or involution stages, the incidence of metastases dropped to 0–10%. Importantly, tumor cells injected into the mammary gland of nude mice grew robustly with 100% take. Nude hosts lack T cells and NKT cells; however, NK cells are present. Furthermore, the liver is enriched for NK cells, whilst the mammary gland has few NK cells.5 We hypothesized that NK cells, when in the background of T- and NKT-cell depletion (i.e. nude host), restrict outgrowth of mammary tumor cells in the liver. Six weeks after portal vein injection of mammary tumor cells to nude hosts we find increased incidence of metastasis in the NK-depleted group compared to isotype control, as well as increased number of metastases per mouse.ConclusionsOur data suggest that NK cells play an important role in controlling liver metastases in nude hosts, and that NK activity in wild type hosts is insufficient to control liver metastases. Increasing NK cell cytotoxic activity could be an effective immunotherapy strategy to control liver metastases.ReferencesNordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, et al: Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013;14(12):1208–1215.Bilen MA, Shabto JM, Martini DJ, Liu Y, Lewis C, Collins H, Akce M, Kissick H, Carthon BC, Shaib WL, et al: Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy. BMC Cancer 2019;19(1):857.Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Sosman JA, Atkins MB, Leming PD, et al: Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab. JAMA Oncol 2019.Goddard ET, Hill RC, Nemkov T, D’Alessandro A, Hansen KC, Maller O, Mongoue-Tchokote S, Mori M, Partridge AH, Borges VF, et al: The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis. Cancer Discov 2017;7(2):177–187.Shi FD, Ljunggren HG, La Cava A, Van Kaer L. Organ-specific features of natural killer cells. Nat Rev Immunol 2011;11(10):658–671.

Tumor Cell-Associated Tissue Factor Supports Metastatic Potential through Both NK Cell-Dependent and -Independent Mechanisms.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 66-66 ◽  
Author(s):  
Joseph Palumbo ◽  
Kelley A. Barney ◽  
Matthew J. Flick ◽  
Kathryn E. Talmage ◽  
Keith W. Kombrinck ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tissue Factor ◽  
Tumor Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Metastatic Potential ◽  
Hemostatic System ◽  
Hemostatic Factors

Abstract Multiple lines of evidence indicate that the hemostatic system contributes to cancer dissemination. Previous studies have shown that tumor cell-associated tissue factor (TF) expression is a crucial determinant of metastatic potential. Furthermore, we have shown that tumor cell-associated TF supports metastatic potential through mechanism(s) dependent on multiple circulating hemostatic system components, including prothrombin, platelets, fibrinogen and, more recently, fXIII. At least two of these circulating hemostatic factors (platelets and fibrinogen) have been shown to support metastatic potential by impeding the clearance of recently embolized tumor cells by natural killer (NK) cells. It is reasonable to hypothesize that tumor cell-associated TF expression also supports metastatic potential by a mechanism coupled to NK cell function. Here, we used C57BL/6-derived, Ras-transformed tumor cell lines expressing wildtype murine tissue factor (TFWT), a mutant TF lacking the intracytoplasmic portion (TFΔTail), or no tissue factor (TFO) to directly examine the interplay between tumor cell-associated TF and NK cell function in determining metastatic potential. Each of these cell lines was capable of robust, comparable tumor growth in wildtype C57BL/6 mice. Loss of either platelet function or fibrinogen significantly diminished the metastatic potential of TFWT cells, but this effect was entirely abrogated by the concomitant loss of NK cells. Similar results were obtained with TFΔTail cells, indicating that the cytoplasmic portion of TF is not critical to these interactions. To determine if the increase in metastatic potential conferred by tumor cell-associated TF expression is entirely linked to NK cell function, we compared the metastatic potential and early survival of TFWT and TFO cells in mice with and without NK cells. TFOcells rarely formed any visible metastatic foci in mice with intact NK cell function, while TFWT cells were aggressively metastatic. Importantly, TF expression remained a significant determinant of metastatic potential even in mice lacking NK cells. Comparisons of the early fate of TFWT and TFO cells revealed that TF expression was not a determinant of initial tumor cell localization within the lungs. Rather, TF expression supported the sustained adherence and/or survival of tumor cells. Taken together, these data indicate that one mechanism linking tumor cell-associated TF expression to metastatic potential is coupled to circulating hemostatic factors and results in impaired NK cell-mediated clearance of recently established micrometastatic foci. However, TF expression also supports metastasis by at least one additional mechanism that is independent of natural killer cell function.

scholarly journals Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis.

1982 ◽  
Vol 156 (2) ◽  
pp. 492-505 ◽  
Author(s):  
S L Helfand ◽  
J Werkmeister ◽  
J C Roder
Keyword(s):  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Target Cell ◽  
Nk Cell ◽  
Target Antigen ◽  
Target Cells ◽  
Tumor Cell Lines

The binding of tumor cells or fetal fibroblasts to human natural killer (NK) cells led to a rapid chemiluminescence response within seconds of target-effector interaction. The degree of chemiluminescence was dependent on the concentration of NK-enriched lymphocytes or target cells, and plasma membrane vesicles from K562 also induced a chemiluminescence response. Mild glutaraldehyde treatment of effector cells abrogated their ability to generate chemiluminescence, whereas K562 target cells treated in the same way were almost fully able to induce a chemiluminescence response to NK-enriched lymphocytes. These results show a directionality of response with NK as the responders and tumor cells as the stimulators. A survey of eight different tumor cell lines and fetal fibroblast lines revealed a striking correlation (r greater than 0.93, P less than 0.001) between the ability of a given line to bind to NK-enriched lymphocytes, induce chemiluminescence, and to be lysed. Three differentiated sublines of K562 grown in butyrate and cloned induced little chemiluminescence compared with the K562 parent, and they were selectively resistant to NK-mediated binding and cytolysis. In addition, treatment of K562 cells with higher concentrations of glutaraldehyde for longer periods led to varying degrees of target antigen preservation, as measured in cold target competition assays and in conjugate formation. The degree of NK target antigen preservation correlated directly with the ability of the cells to induce chemiluminescence (r greater than 0.95). The degree of NK activation was also important because interferon-pretreated effectors generated more chemiluminescence upon stimulation with K562 or MeWo targets. Monocytes or granulocytes did not contribute to the chemiluminescence induced by NK-sensitive targets. Some NK-resistant tumor cell lines were sensitive to monocyte-mediated cytolysis and also induced chemiluminescence in monocytes but not NK cells. These results show that the target structures recognized by the NK cell may play a role in NK activation because the degree of chemiluminescence was directly proportional to the ability of a given target cell line to bind to the NK cell and to be lysed.

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