Natural Killer Cells in
Human Cancer
Source: Biochimica et
Biophysica Acta, 865: 329-240, 1986
The journal article summarizes various
research regarding what is currently known about natural killer cell function and then
describes their important role in cancer prevention and cancer removal. Written by
the Department of Immunology, Smith Kline & French Laboratories, Philadelphia, PA,
this information should be of special interest to parents of children with brain cancer,
neuroblastoma and leukemia as these cancers have been found to be associated with
defective natural killer cell function. The following are direct quotes regarding
major points from the article.
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"Moreover, the
efficacy of the different host defense mechanisms in destroying malignant cells may depend
upon the extent of tumor burden, immunogenicity and site of tumor growth. For
example, certain immune and nonimmune mechanisms may prove effective in destroying
circulating tumor cells even though they might exert only a limited effect against the
extravascular primary neoplasm. This may be attributed to the observation that
unlike the cells within a solid tumor, tumor cells enter the circulation as single cells
or small clumps and are, therefore, highly accessible and more vulnerable to destruction
by immune and non-immune defense mechanisms." pg. 214
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"Indeed, most tumor
cells that enter the circulation are destroyed during the first 24 h and only a few cells
succeed to extravasate and develop into metastatic foci in the organ parenchyma."
pg. 214
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Also, the incidence of
spontaneous malignant lymphomas was reported to be increased in NK-deficient mice carrying
the beige mutation. In contrast, the relatively low incidence of tumor development
in athymic nude mice that exhibit high NK cell-mediated cytotoxicity suggested that a T
cell-independent mechanism may be operative in immunosurveillance." pg. 214
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Virtually all NK
cell activity in humans is mediated by large granular lymphocytes (LGL) which
represent 5-10% of peripheral blood mononuclear cells." pg. 215
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NK cells express
receptors to IL-2 (interleukin 2) and can proliferate in response to T cell mitogens
and IL-2." pg. 215
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NK cells originate in
the bone marrow and exhibit a characteristic organ distribution, their activity being
highest in peripheral blood and then, in descending order, spleen, lymph nodes and bone
marrow, and absent in the thymus." pg. 215
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...NK cells and/or their
precursors are highly sensitive to treatment in vivo with cyclophosphamide, B-estradiol
and Sr. Animals treated with such agents and the beige mouse exhibit low levels of
NK cell activity and provide valuable models for studying the in vivo role of NK cells in
host defense against neoplasms." pg. 215
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Also, depletion of NK
cells in vivo by treatment with antiasialo-GM1 antibodies (antibodies injected to remove
natural killer cells) resulted in increased tumorogenicity and percent takes of NK
sensitive tumor cells transplanted into syngeneic and nude mice." pg. 216
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Also, it should be
emphasized that NK-mediated resistance against tumor growth in vivo was expressed
only when a small number of tumor cells were inoculated. Therefore, it was
concluded that NK cells serve as a rapidly acting first-line defense mechanism that is
involved in the early destructive events following tumor implantation."
pg. 216
CHEM-TOX COMMENT:
This last statement provides a biological explanation why cancers would develop
more rapidly in children living in proximity to chemical sources which can suppress
natural killer cell function (i.e. agriculture areas, home pesticide & chemical use,
etc.)
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Activation of NK cells
may be easily achieved by treatment with interferon, interferon inducers, interleukin-2
and bacterial adjuvants." pg. 219
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During surgical
manipulation of the primary tumor, potential malignant cells may be released into
the circulation and develop into secondary metastatic foci. " pg. 224
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Moreover, the
suppressive effects of surgery and anesthesia on NK cell activity may further facilitate
the survival of tumor cells released from the primary or metastatic tumor growth and
contribute to the increased incidence of metastasis. Therefore, certain BRM,
including low doses of interferon, may prove safe and, if appropriate applied, effective
in preventing further tumor dissemination and metastasis." pg. 226
CHEM-TOX COMMENT: Exposure to anesthethesia compounds have been found to weaken immune system
function which also explains the high incidence of infection following anesthesia
exposure.
Department of
Immunology, Smith Kline & French Laboratories
1500 Spring Garden Street, Philadelphia, PA 19101
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