NK Cells for cancer patients

What is Natural Killer (NK) Cells?

Natural Killer (NK) cells are a type of cytotoxic lymphocyte and a crucial component of the innate immune system. Unlike T and B cells, NK cells do not possess antigen-specific receptors and can therefore recognize and kill target cells without prior sensitization. They are characterized by the expression of specific surface markers, such as CD56 and CD16, and play a vital role in early immune responses against viral infections and cancerous cells. NK cells originate and mature in the bone marrow and then circulate in the blood and reside in various tissues.

How do NK Cells Fight Cancer?

NK cells employ several mechanisms to eliminate cancer cells. One primary mechanism involves the release of cytotoxic granules containing perforin and granzymes. Perforin creates pores in the target cell membrane, allowing granzymes to enter and induce apoptosis, or programmed cell death. Another crucial mechanism is antibody-dependent cell-mediated cytotoxicity (ADCC). NK cells express the CD16 (FcγRIII) receptor, which binds to the Fc region of antibodies that have opsonized cancer cells. This binding triggers the release of cytotoxic granules directly at the surface of the cancer cell, leading to its destruction. Furthermore, NK cells express activating and inhibitory receptors that recognize ligands on target cells. The balance of signals received through these receptors determines whether an NK cell will kill a target cell. Cancer cells often alter the expression of these ligands, making them susceptible to NK cell-mediated killing.

How do NK Cells Boost Cancer Patients' Immune Systems?

Beyond directly killing cancer cells, NK cells contribute to boosting the overall immune response in cancer patients. They produce various cytokines and chemokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which play critical roles in modulating the activity of other immune cells, including dendritic cells, macrophages, and T cells. IFN-γ, for instance, enhances the antigen-presenting capacity of dendritic cells, promoting the activation of antigen-specific T cells that can further target cancer cells. NK cells can also directly interact with dendritic cells, influencing their maturation and their ability to initiate adaptive immune responses. By releasing these signaling molecules and interacting with other immune cells, NK cells help to create a more robust and coordinated anti-tumor immune response.

NK cells utilize a sophisticated system of activating and inhibitory receptors to distinguish between healthy cells and abnormal cells like cancer cells. Healthy cells express high levels of major histocompatibility complex class I (MHC class I) molecules, which are recognized by inhibitory receptors on NK cells, such as KIRs (killer cell immunoglobulin-like receptors) and CD94/NKG2A. This interaction delivers a "don't kill me" signal, preventing NK cells from attacking normal cells. However, cancer cells often downregulate or lose MHC class I expression as a mechanism to evade detection by cytotoxic T lymphocytes. This reduced MHC class I expression renders cancer cells "missing self," making them susceptible to recognition and killing by NK cells because the inhibitory signal is diminished. Additionally, cancer cells frequently upregulate the expression of stress-induced ligands, such as MICA, MICB, and ULBPs, which are recognized by activating receptors like NKG2D on NK cells. The engagement of these activating receptors, in the absence of strong inhibitory signals, triggers NK cell activation and cytotoxicity against the cancer cell. This balance between activating and inhibitory signals allows NK cells to selectively target and eliminate aberrant cells while sparing healthy ones.