In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell, consisting mostly of natural killer, natural killer T, and T cells that has been stimulated to kill tumor cells, but because of the function in which they activate, and the cells they can successfully target, they are classified as different than the classical natural killer and T lymphocyte systems.
Mechanism
It has been shown that when Peripheral blood leukocytes (PBL) are cultured in the presence of Interleukin 2, it results in the development of effector cells, which are cytotoxic and are seen to localize to tumor sites and are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic.[1] LAK cells respond to these lymphokines, particularly IL-2, by developing into effector cells capable of lysing tumor cells that are known to be resistant to NK cell activity. After stimulated by IL-2, LAK cells can target and kill tumor cells in the early innate response.[2]
The mechanism of LAK cells is distinctive from that of natural killer cell because they can lyse cells that an NK cell cannot. LAK cells are also capable of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors. LAK cells function in the same way as NK cells in the peripheral blood but are more sensitive to and can target tumor cells.
Cancer Treatment
The use of LAK cells has been found to be helpful in treating human cells with different cancers in vitro[3]. LAK cell therapy is a method that uses interleukin 2 (IL-2) to enhance the number of lymphocytes in an in vitro setting, and it has formed the foundation of many immunotherapy assays that are now in use.[4] LAK cells have shown potential as a cellular agent for cancer therapy and have been utilized therapeutically in association with IL-2 for the treatment of various cancers. LAK cells have anticancer efficacy against homologous carcinoma cells and can grow ex vivo in the presence of IL-2.[5] In melanoma and gastric cancer cells, intercellular adhesion molecule 1 (ICAM-1) antibody can significantly inhibit in vitro LAK-induced lysis of cancer cells. A study has shown that ICAM1 in lung cancer cells increases LAK cell-mediated tumor cell death as a new anti-tumor mechanism.[6] One study uses a 4 hour chromium release assay, which is an assay used to measure the cytotoxicity of T cells and natural killer cells, to measure lysis of the fresh solid tumor cells from 10 cancer patients and found that in all 10 cancer patients the fresh autologous tumor cells were resistant to lysis by PBL with natural killer cells, but were lysed by the LAK cells.[2]
Treatment Possible Side Effects
LAK cells, along with the administration of IL-2 have been experimentally used to treat cancer in mice and humans, but there is very high toxicity with this treatment - Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Treatment of IL-2 cells by themselves to treat cancers are more dangerous than treatment with the combination of IL-2 and LAK cells.[7]
^Haustein M, Ramer R, Linnebacher M, Manda K, Hinz B (November 2014). "Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1". Biochem Pharmacol. 92 (2): 312–25. doi:10.1016/j.bcp.2014.07.014. PMID25069049.
