What Are Natural Killer Cells?

The Power of NK Cells

How Do NK Cells Work & Why Are They Important?

Natural Killer (NK) cells are cytotoxic lymphocytes that play a critical role in the innate immune system—the body’s first line of defense, present from birth. NK cells act as the immune system’s rapid-response force, targeting and destroying virally infected cells and identifying early signs of cancer to prevent tumor development and spread. As a subset of white blood cells called lymphocytes—which also includes B cells and T cells—NK cells account for approximately 5% to 15% of circulating lymphocytes and have a relatively short lifespan of about two weeks.


Unlike adaptive immune cells, NK cells can recognize and eliminate threats without prior sensitization. This "natural" ability allows them to respond swiftly to a wide range of pathological challenges, making them a powerful tool in immunotherapy. In contrast, T and B cells of the adaptive immune system require prior exposure to specific pathogens to mount an effective response.




NKs vs. Cancer

NK Cells Role Against Cancer

NK cells are known to be critical in the fight against cancer. While T-cells have been the primary focus of cancer immunotherapy, it is recognized that in the prevention of metastases through the elimination of circulating cancer stem cells with high metastatic potential, NK cells are the main immune effector cells. This is due to their unique ability to identify and spontaneously kill poorly differentiated cancer stem and stem-like cells that do not express MHC class I on their surface without prior sensitization. Given the propensity of solid tumors to down-regulate the surface expression of MHC class I, this unique function of NK cells is critical in those circumstances where cytotoxic T-cells, which require MHC class I for tumor recognition and elimination, are incapable of mounting an immune response.


While an NK cell’s primary job is killing infected and cancerous cells, these immune cells are also capable of releasing cytokines and chemokines, including gamma interferon (IFN-y) and tumor necrosis factor alpha (TNFa), that promote an inflammatory immune response and play an important role in regulating T-cells and other adaptive immune cells to mount an immune response and attack harmful cells and pathogens.


In addition, it has been recently proposed that NK cells also exhibit a crucial role in the control of metastasis by eliminating circulating cancer cells with stem-like cell characteristics. Cancer stem cells (CSCs) are a subpopulation of tumor cells sharing similar characteristics as normal stem or progenitor cells, such as self-renewal ability and multi-lineage differentiation. Their presence is recognized as a crucial factor contributing to tumor progression and metastasis. Conventional cancer treatments target the bulk of the tumor but are unable to target CSCs due to their highly resistant nature, leading to tumor recurrence and metastasis. Considering these findings, eradicating or differentiating (and thus eliminating their self-renewal ability) the CSC subpopulation is a potential strategy for cancer treatment (Source: Molecular Cancer, Vol. 22 (171), 2023).


NK cells play a dual role in the elimination of CSCs. NK cells have been shown to selectively kill CSCs as well as eliminate circulating cancer cells with stem-like cell characteristics, a crucial role in the control of metastasis. In addition, NK’s secretion of functional IFN-γ can induce CSCs differentiation, resulting in CSCs eradication and decreasing the possibility of recurrence and metastasis (Source: Communications Biology, Vol. 5 (436), 2022). 



Function of Primary Natural Killer Cells

Natural defense mechanism attacks cancer stem cells and secrete IFNy and TNFa; what makes them unique

Primary NK cells (pNK cells) are cytotoxic lymphocytes that act as our natural defense mechanism against cancer and other immune system disorders.


pNK Cells:

  • Comprise 5-15% of our peripheral white blood cells
    mononuclear cells.
  • Critical function to control tumors:
  1. Cytotoxic: direct killing or antibody-dependent cellular cytotoxicity (ADCC) in tumors

  2. Cytokine secretion: NK cells secrete interferon-gamma (IFNy) and tumor necrotic factor-alpha (TNFa) that play a role in tumor differentiation & trigger specific responses, such as inflammation, immunity, or tissue repair
  • Direct killing by freshly isolated IL-2 treated NK cells in oral squamous cancer stem cells (OSCSCs).
  • Propidium iodide is expressed upon cell death resulting in red glow.

Supercharged NKs vs Other NK Cell Therapies

Improved Potency | Improved Robustness

Functional Characteristics of sNK cells:


  • Enhances cytotoxic function (killing)

  • Increased secretion of IFN-γ and TNF- α expected to induce differentiation and reduce the metastatic potential of the tumor cells
  • Improved ability to better withstand the suppressive tumor microenvironment

  • Increased efficacy to inhibit tumor growth and metastasis and also, the potential to restore immune function.


Above / Ovarian Cancer Cells Being Treated by Various NK Therapies :

1. Tumor Alone / shows how cancer will quickly grow when no NK cells are present

2. +pNK+IL2+anti-CD16 / shows how a cytokine and IL2 activated NK therapy does very little to kill the cancer

3. +pNK + IK2 /  shows how IL2 activated NKs do a better job of killing the cancer but it does not fully eliminate it

4. +sNK /  shows how NKore's sNK therapy, NK101, causes the cancer cells to clump together, wither and die