Human natural killer cells: a comprehensive review

Area of Science:

• Immunology
• Evolutionary Biology
• Cancer Research

Background:

• Initial observations in 1969 revealed lymphocytes with cytotoxic activity against allogeneic tumor cells in vitro.
• These findings were initially met with skepticism, attributed to in vitro artifacts, contrasting with established tumor-specific cytotoxicity assays.
• Subsequent research funded by the National Cancer Institute (NCI) characterized these cytotoxic lymphocytes as natural killer (NK) cells.

Purpose of the Study:

• To review original observations of lymphocyte-mediated cytotoxicity from 1969-1971 in light of recent discoveries.
• To explain the evolutionary history and functional roles of NK cells across different species.
• To explore the therapeutic potential of NK cells, particularly as lymphokine-activated killer (LAK) cells, in cancer treatment.

Main Methods:

• Review of preserved original research materials from 1969-1971.
• Integration of recent discoveries in NK cell biology and immunology.
• Clinical application of LAK cells and Interleukin-2 (IL-2) for adoptive immunotherapy.

Main Results:

• NK cells evolved from early defense mechanisms in urochordates to integrated roles in adaptive immunity and mammalian reproduction.
• Tumors can induce immune-tolerant reactions in NK cells, similar to fetal-maternal interactions, but NK cells can overcome this tolerance.
• LAK cell therapy, utilizing IL-2, showed efficacy in treating metastatic melanoma, kidney carcinoma, and ovarian carcinoma, with one patient achieving remission.

Conclusions:

• NK cells possess a rich evolutionary history and diverse functions, including tumor surveillance.
• NK cells can be therapeutically enhanced (e.g., LAK cells) for cancer immunotherapy.
• NK cells, like dendritic cells, can undergo malignant transformation, leading to lymphoma-leukemia, as exemplified by reported cases.