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

E. A. Grimm, A. Mazumder, H. Z. Zhang, S. A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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 OKT3, 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.

Original languageEnglish (US)
Pages (from-to)1823-1841
Number of pages19
JournalJournal of Experimental Medicine
Volume155
Issue number6
StatePublished - 1982
Externally publishedYes

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Lymphokine-Activated Killer Cells
Interleukin-2
Lymphokines
Mononuclear Leukocytes
Lymphocytes
Neoplasms
Natural Killer Cells
Monocytes
Muromonab-CD3
Thoracic Duct
Lectins
Interferons
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

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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. / Grimm, E. A.; Mazumder, A.; Zhang, H. Z.; Rosenberg, S. A.

In: Journal of Experimental Medicine, Vol. 155, No. 6, 1982, p. 1823-1841.

Research output: Contribution to journalArticle

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