Lymphokine-activated killer cell phenomenon. Lysis of natural killer- resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes

doi:10.1084/jem.155.6.1823

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Lymphokine-activated killer cell phenomenon. Lysis of natural killer- resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes

EA Grimm, A Mazumder, HZ Zhang and SA Rosenberg

Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK- resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon- depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.
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Gilman, A. L., Ozkaynak, M. F., Matthay, K. K., Krailo, M., Yu, A. L., Gan, J., Sternberg, A., Hank, J. A., Seeger, R., Reaman, G. H., Sondel, P. M. (2009). Phase I Study of ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2 in Children With Neuroblastoma After Autologous Bone Marrow Transplantation or Stem-Cell Rescue: A Report From the Children's Oncology Group. JCO 27: 85-91 [Abstract] [Full Text]
Wu, Z., Xue, H.-H., Bernard, J., Zeng, R., Issakov, D., Bollenbacher-Reilley, J., Belyakov, I. M., Oh, S., Berzofsky, J. A., Leonard, W. J. (2008). The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15R{alpha} function but is not required for trans-presentation. Blood 112: 4411-4419 [Abstract] [Full Text]
Kirkwood, J. M., Tarhini, A. A., Panelli, M. C., Moschos, S. J., Zarour, H. M., Butterfield, L. H., Gogas, H. J. (2008). Next Generation of Immunotherapy for Melanoma. JCO 26: 3445-3455 [Abstract] [Full Text]
Chlewicki, L. K., Velikovsky, C. A., Balakrishnan, V., Mariuzza, R. A., Kumar, V. (2008). Molecular Basis of the Dual Functions of 2B4 (CD244). J. Immunol. 180: 8159-8167 [Abstract] [Full Text]
Mignot, G., Ullrich, E., Bonmort, M., Menard, C., Apetoh, L., Taieb, J., Bosisio, D., Sozzani, S., Ferrantini, M., Schmitz, J., Mack, M., Ryffel, B., Bulfone-Paus, S., Zitvogel, L., Chaput, N. (2008). The Critical Role of IL-15 in the Antitumor Effects Mediated by the Combination Therapy Imatinib and IL-2. J. Immunol. 180: 6477-6483 [Abstract] [Full Text]
Markovic, S. N., Erickson, L. A., Rao, R. D., Weenig, R. H., Pockaj, B. A., Bardia, A., Vachon, C. M., Schild, S. E., McWilliams, R. R., Hand, J. L., Laman, S. D., Kottschade, L. A., Maples, W. J., Pittelkow, M. R., Pulido, J. S., Cameron, J. D., Creagan, E. T., Melanoma Study Group of the Mayo Clinic Cancer Cen, (2007). Malignant Melanoma in the 21st Century, Part 2: Staging, Prognosis, and Treatment. Mayo Clin Proc. 82: 490-513 [Abstract] [Full Text]
Hirose, Y., Murosaki, S., Yamamoto, Y., Yoshikai, Y., Tsuru, T. (2006). Daily Intake of Heat-Killed Lactobacillus plantarum L-137 Augments Acquired Immunity in Healthy Adults. J. Nutr. 136: 3069-3073 [Abstract] [Full Text]
Varker, K. A., Kondadasula, S. V., Go, M. R., Lesinski, G. B., Ghosh-Berkebile, R., Lehman, A., Monk, J. P., Olencki, T., Kendra, K., Carson, W. E. III (2006). Multiparametric Flow Cytometric Analysis of Signal Transducer and Activator of Transcription 5 Phosphorylation in Immune Cell Subsets In vitro and following Interleukin-2 Immunotherapy.. Clin. Cancer Res. 12: 5850-5858 [Abstract] [Full Text]
Ebata, K., Shimizu, Y., Nakayama, Y., Minemura, M., Murakami, J., Kato, T., Yasumura, S., Takahara, T., Sugiyama, T., Saito, S. (2006). Immature NK Cells Suppress Dendritic Cell Functions during the Development of Leukemia in a Mouse Model. J. Immunol. 176: 4113-4124 [Abstract] [Full Text]
Feng, Y., Huang, N., Wu, Q., Wang, B. (2005). HMGN2: a novel antimicrobial effector molecule of human mononuclear leukocytes?. J. Leukoc. Biol. 78: 1136-1141 [Abstract] [Full Text]
Schwinger, W., Klass, V., Benesch, M., Lackner, H., Dornbusch, H. J., Sovinz, P., Moser, A., Schwantzer, G., Urban, C. (2005). Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer patients. Ann Oncol 16: 1199-1206 [Abstract] [Full Text]
Kojima, H., Kanno, Y., Hase, H., Kobata, T. (2005). CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation. J. Immunol. 174: 5959-5967 [Abstract] [Full Text]
Takeda, K., Okumura, K. (2004). CAM and NK Cells. Evid Based Complement Alternat Med 1: 17-27 [Abstract] [Full Text]
Beider, K., Nagler, A., Wald, O., Franitza, S., Dagan-Berger, M., Wald, H., Giladi, H., Brocke, S., Hanna, J., Mandelboim, O., Darash-Yahana, M., Galun, E., Peled, A. (2003). Involvement of CXCR4 and IL-2 in the homing and retention of human NK and NK T cells to the bone marrow and spleen of NOD/SCID mice. Blood 102: 1951-1958 [Abstract] [Full Text]
Feinmesser, R., Hardy, B., Sadov, R., Shwartz, A., Chretien, P., Feinmesser, M. (2003). Report of a Clinical Trial in 12 Patients With Head and Neck Cancer Treated Intratumorally and Peritumorally With Multikine. Arch Otolaryngol Head Neck Surg 129: 874-881 [Abstract] [Full Text]
Epstein, A. L., Mizokami, M. M., Li, J., Hu, P., Khawli, L. A. (2003). Identification of a Protein Fragment of Interleukin 2 Responsible for Vasopermeability. JNCI J Natl Cancer Inst 95: 741-749 [Abstract] [Full Text]
Robertson, M. J. (2002). Role of chemokines in the biology of natural killer cells. J. Leukoc. Biol. 71: 173-183 [Abstract] [Full Text]
Clarke, R., Leonessa, F., Welch, J. N., Skaar, T. C. (2001). Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance. Pharmacol. Rev. 53: 25-72 [Abstract] [Full Text]
Pedersen, B. K., Hoffman-Goetz, L. (2000). Exercise and the Immune System: Regulation, Integration, and Adaptation. Physiol. Rev. 80: 1055-1081 [Abstract] [Full Text]
Shallal, S., Kornbluth, J. (2000). CD9 expression enhances the susceptibility of myeloma cell lines to cell-mediated cytolysis. Blood 96: 224-233 [Abstract] [Full Text]
Steele, T. A. (2000). Recent Developments in the Virus Therapy of Cancer. Exp. Biol. Med. 223: 118-127 [Abstract] [Full Text]
Shimizu, J., Yamazaki, S., Sakaguchi, S. (1999). Induction of Tumor Immunity by Removing CD25+CD4+ T Cells: A Common Basis Between Tumor Immunity and Autoimmunity. J. Immunol. 163: 5211-5218 [Abstract] [Full Text]
O'HEARN, D. J., LEIFERMAN, K. M., ASKIN, F., GEORAS, S. N. (1999). Pulmonary Infiltrates after Cytokine Therapy for Stem Cell Transplantation . Massive Deposition of Eosinophil Major Basic Protein Detected by Immunohistochemistry. Am. J. Respir. Crit. Care Med. 160: 1361-1365 [Abstract] [Full Text]
Cantoni, C., Bottino, C., Vitale, M., Pessino, A., Augugliaro, R., Malaspina, A., Parolini, S., Moretta, L., Moretta, A., Biassoni, R. (1999). NKp44, A Triggering Receptor Involved in Tumor Cell Lysis by Activated Human Natural Killer Cells, Is a Novel Member of the Immunoglobulin Superfamily. JEM 189: 787-796 [Abstract] [Full Text]
Lustgarten, J., Marks, J., Sherman, L. A. (1999). Redirecting Effector T Cells Through Their IL-2 Receptors. J. Immunol. 162: 359-365 [Abstract] [Full Text]
Bradley, M., Zeytun, A., Rafi-Janajreh, A., Nagarkatti, P. S., Nagarkatti, M. (1998). Role of Spontaneous and Interleukin-2-Induced Natural Killer Cell Activity in the Cytotoxicity and Rejection of Fas+ and Fas- Tumor Cells. Blood 92: 4248-4255 [Abstract] [Full Text]
Liu, S.-J., Sher, Y.-P., Ting, C.-C., Liao, K.-W., Yu, C.-P., Tao, M.-H. (1998). Treatment of B-Cell Lymphoma With Chimeric IgG and Single-Chain Fv Antibody-Interleukin-2 Fusion Proteins. Blood 92: 2103-2112 [Abstract] [Full Text]
YONEDA, T., ELLNER, J.�J. (1998). CD4+ T Cell and Natural Killer Cell-dependent Killing of Mycobacterium tuberculosis by Human Monocytes. Am. J. Respir. Crit. Care Med. 158: 395-403 [Abstract] [Full Text]
Matsumoto, G., Nghiem, M. P., Nozaki, N., Schmits, R., Penninger, J. M. (1998). Cooperation Between CD44 and LFA-1/CD11a Adhesion Receptors in Lymphokine-Activated Killer Cell Cytotoxicity. J. Immunol. 160: 5781-5789 [Abstract] [Full Text]
Lode, H. N., Xiang, R., Dreier, T., Varki, N. M., Gillies, S. D., Reisfeld, R. A. (1998). Natural Killer Cell-Mediated Eradication of Neuroblastoma Metastases to Bone Marrow by Targeted Interleukin-2 Therapy. Blood 91: 1706-1715 [Abstract] [Full Text]
Zhang, R., Minemura, K., De Groot, L. J. (1998). Immunotherapy for Medullary Thyroid Carcinoma by a Replication-Defective Adenovirus Transducing Murine Interleukin-2. Endocrinology 139: 601-608 [Abstract] [Full Text]
Maria, B. L., Medina, C. D., Hoang, K. B.N., Phillips, M. I. (1997). Topical Review: Gene Therapy for Neurologic Disease: Benchtop Discoveries to Bedside Applications. 1. The Bench. J Child Neurol 12: 1-12 [Abstract]
Fujieda, S., Noda, I., Saito, H., Hoshino, T., Yagita, M. (1995). Heat Shock Enhances the Susceptibility of Tumor Cells to Lysis by Lymphokine-Activated Killer Cells. Arch Otolaryngol Head Neck Surg 121: 1009-1014 [Abstract]
Cunningham-Rundles, C., Kazbay, K., Hassett, J., Zhou, Z., Mayer, L. (1994). Enhanced Humoral Immunity in Common Variable Immunodeficiency after Long-Term Treatment with Polyethylene Glycol-Conjugated Interleukin-2. NEJM 331: 918-921 [Full Text]
Fujieda, S., Noda, I., Saito, H., Hoshino, T., Yagita, M. (1994). Swainsonine Augments the Cytotoxicity of Human Lymphokine-Activated Killer Cells Against Autologous Thyroid Cancer Cells. Arch Otolaryngol Head Neck Surg 120: 389-394 [Abstract]
Rosenberg, S. A., Yang, J. C., Topalian, S. L., Schwartzentruber, D. J., Weber, J. S., Parkinson, D. R., Seipp, C. A., Einhorn, J. H., White, D. E. (1994). Treatment of 283 Consecutive Patients With Metastatic Melanoma or Renal Cell Cancer Using High-Dose Bolus Interleukin 2. JAMA 271: 907-913 [Abstract]
Takahashi, H, Nakada, T, Puisieux, I (1993). Inhibition of human colon cancer growth by antibody-directed human LAK cells in SCID mice. Science 259: 1460-1463 [Abstract]
Johnkoski, J. A., Tzung, S.-P., Doerr, R. J., Cohen, S. A. (1992). Hepatic Metastasis Alters the Immune Function of Murine Liver Nonparenchymal Cells. Arch Surg 127: 1325-1329 [Abstract]
Dummer, R., Becker, J. C., Boser, B., Hartmann, A. A., Burg, G. (1992). Successful Therapy of Metastatic Eccrine Poroma Using Perilesional Interferon Alfa and Interleukin 2. Arch Dermatol 128: 1127-1128 [Abstract]
Clayman, G. L., Liu, F. J., Savage, H. E., Taylor, D. L., Lavedan, P., Buchsbaum, R. M., Pellegrino, C., Trujillo, J. M., Young, G., Schantz, S. P. (1992). Acute-Phase Proteins in Patients With Head and Neck Cancer Treated With Interleukin 2/Interferon Alfa. Arch Otolaryngol Head Neck Surg 118: 41-48 [Abstract]
Horn, T. D., Rest, E. B., Karp, J. E., Burke, P. J., Vogelsang, G. B., Boucher, C. L., Hood, A. F. (1991). Interleukin 2 and Granulocyte-Macrophage Colony-Stimulating Factor Induce a Perivascular Lymphocytic Infiltrate in a Skin Explant Model. Arch Dermatol 127: 1789-1793 [Abstract]
Pelton, J. J., Taylor, D. D., Fowler, W. C., Taylor, C. G., Carp, N. Z., Weese, J. L. (1991). Lymphokine-Activated Killer Cell Suppressor Factor in Malignant Effusions. Arch Surg 126: 476-480 [Abstract]
Wood, N. L., Kitces, E. N., Blaylock, W. K. (1990). Depressed Lymphokine Activated Killer Cell Activity in Mycosis Fungoides: A Possible Marker for Aggressive Disease. Arch Dermatol 126: 907-913 [Abstract]
Hatakeyama, M, Tsudo, M, Minamoto, S, Kono, T, Doi, T, Miyata, T, Miyasaka, M, Taniguchi, T (1989). Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science 244: 551-556 [Abstract]
Eberlein, T. J., Schoof, D. D., Michie, H. R., Massaro, A. F., Burger, U., Wilmore, D. W., Wilson, R. E. (1989). Ibuprofen Causes Reduced Toxic Effects of Interleukin 2 Administration in Patients With Metastatic Cancer. Arch Surg 124: 542-547 [Abstract]
ROSENBERG, S. A., LOTZE, M. T., MULE, J. J. (1988). New Approaches to the Immunotherapy of Cancer Using Interleukin-2. ANN INTERN MED 108: 853-864 [Abstract]
Lindemann, R.A., Miyasaki, K.T., Wolinsky, L.E. (1988). Induction of Activated Lymphocyte Killing by Bacteria Associated with Periodontal Disease. JDR 67: 846-850 [Abstract]
FISHER, R. I., COLTMAN, C. A. Jr., DOROSHOW, J. H., RAYNER, A. A., HAWKINS, M. J., MIER, J. W., WIERNIK, P., MCMANNIS, J. D., WEISS, G. R., MARGOLIN, K. A., GEMLO, B. T., HOTH, D. F., PARKINSON, D. R., PAIETTA, E. (1988). Metastatic Renal Cancer Treated with Interleukin-2 and Lymphokine-Activated Killer Cells: A Phase II Clinical Trial. ANN INTERN MED 108: 518-523 [Abstract]
Brandhuber, B., Boone, T, Kenney, W., McKay, D. (1987). Three-dimensional structure of interleukin-2. Science 238: 1707-1709 [Abstract]
Lindemann, R.A., Golub, S.H., Park, N.-H. (1987). HSV-1-infected Oral Epithelial Cells are Targets for Natural Killer Cells. JDR 66: 770-773 [Abstract]
FAUCI, A. S., ROSENBERG, S. A., SHERWIN, S. A., DINARELLO, C. A., LONGO, D. L., LANE, H. C. (1987). Immunomodulators in Clinical Medicine. ANN INTERN MED 106: 421-433 [Abstract]
FAHEY, J. L., SARNA, G., GALE, R. P., SEEGER, R. (1987). Immune Interventions in Disease. ANN INTERN MED 106: 257-274 [Abstract]
Rosenberg, S., Spiess, P, Lafreniere, R (1986). A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233: 1318-1321 [Abstract]
Taniguchi, T., Fujita, T., Hatakeyama, M., Mori, H., Matsui, H., Sato, T., Hamuro, J., Minamoto, S., Yamada, G., Shibuya, H. (1986). Interleukin-2 and Its Receptor: Structure and Functional Expression of the Genes. Cold Spring Harb Symp Quant Biol 51: 577-586 [Abstract]
Mule, J., Shu, S, Schwarz, S., Rosenberg, S. (1984). Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 225: 1487-1489 [Abstract]
Wang, A, Lu, S., Mark, D. (1984). Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science 224: 1431-1433 [Abstract]
Rosenberg, S., Grimm, E., McGrogan, M, Doyle, M, Kawasaki, E, Koths, K, Mark, D. (1984). Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science 223: 1412-1414 [Abstract]