NK cell-based cancer immunotherapy is a promising approach within the realm of cancer treatment, harnessing the power of natural killer (NK) cells to bolster the body’s immune reaction against cancerous cells. As integral components of the innate immune system, NK cells play a pivotal role in identifying and eradicating aberrant or infected cells, including cancer cells, without the need for prior sensitization. Their label as “natural killers” arises from their unique capability to identify and eliminate infected or malignant cells without prior sensitization, setting them apart from adaptive immune counterparts like T cells, which mandate previous exposure to specific antigens.
NK cells constitute approximately 5-10% of circulating lymphocytes and are identified by their distinctive characteristics, characterized by the absence of CD3 and the presence of CD56 surface markers.
These NK cells employ diverse mechanisms to detect and eliminate foreign, damaged, infected, or malignant cells. These immune warriors possess surface receptors that enable differentiation between healthy cells and anomalous cells, such as tumor cells. They can identify specific molecules displayed on the surface of tumor cells, termed stress-induced ligands or tumor-associated antigens.
Typically, healthy cells showcase major histocompatibility complex class I (MHC-I) molecules on their surface. These molecules showcase regular cellular proteins to T cells, preventing the immune system from targeting healthy cells. However, numerous tumor cells downregulate MHC-I expression as an evasion tactic. NK cells detect this MHC-I absence and interpret it as an abnormality signal.
Upon encountering tumor cells or cells with diminished MHC-I expression, NK cells spring into action. Activation hinges on a balance between signals from activating and inhibitory receptors on the NK cell surface. Activating receptors, triggered by the identification of tumor-associated antigens or stress-induced ligands, fuel NK cell activity. Inhibitory receptors, often engaging with MHC-I on healthy cells, temper the NK cell response to normal cells.
Following activation, NK cells unleash cytotoxic substances like perforin and granzymes, forming pores in the tumor cell membrane. This permits granzymes to infiltrate the tumor cell, triggering caspases and instigating apoptosis (cell death). Furthermore, NK cells can secrete cytokines like interferon-gamma, facilitating the recruitment of other immune cells and intensifying the anti-tumor immune response.
Furthermore, natural killer cells are the primary effectors in a process termed antibody-dependent cell-mediated cytotoxicity (ADCC).
Multiple strategies are under exploration for NK cell-based cancer immunotherapy:
- Adoptive NK Cell Therapy: Encompassing Autologous and Allogeneic NK cell therapy.
- CAR-NK Cell Therapy: Involves genetically modifying NK cells to express chimeric antigen receptors (CARs) on their surface.
- NK Cell Engagers: Therapeutic molecules designed to bridge NK cells and cancer cells.
- Combination Therapies: NK cell-based immunotherapies in conjunction with other cancer treatments like checkpoint inhibitors, chemotherapy, or radiation therapy.
Potential contraindications for NK cell therapy could encompass:
- Severe Immunodeficiency
- Pre-existing Autoimmune Disorders
- Allergic Reactions
- Severe Organ Dysfunction
The efficacy of NK cell therapy may be influenced by various factors, including the tumor microenvironment, the patient’s overall health, cancer stage, and specific cancer cell attributes.
Certain cancer types have exhibited greater responsiveness to early-stage NK cell therapy studies, while others may necessitate further research and treatment refinement. Encouraging advancements have emerged in the utilization of NK cell therapy for select solid cancer types, such as Breast Cancer, Lung Cancer, Gastric Cancer, and Colorectal Cancer. Though clinical trials and research have unveiled promising outcomes in specific instances, it’s crucial to recognize that this field’s exploration remains nascent and ongoing.