Journal of Cancer Science and Research
Open Access

Mitochondria's Function in Anti-Tumor Immunity Regulation

Anqo Bejhna^{* *}Correspondence: Anqo Bejhna, Department of Non-communicable Diseases, Kerman University of Medical Sciences, Kerman, Iran, Email:

Author info »

About the Study

Anti-tumor immunity refers to the body's natural defense mechanisms that identify and eliminate cancer cells. The immune system plays an important role in identifying and destroying abnormal cells, including those that can develop into tumors. The regulation of anti-tumor immunity involves a complex interaction of various cellular and molecular mechanisms aimed at recognizing and eliminating cancer cells while maintaining tolerance to normal tissues. While mitochondria are mainly known for their role in energy production, recent research has provided understanding of their involvement in the regulation of immune responses, including anti-tumor immunity. The intersection between mitochondrial function and anti-tumor immunity involves various processes.

Components of the immune system

T cells (T lymphocytes): These are a type of white blood cell that plays a vital role in cell-mediated immunity. T cells can directly kill cancer cells or release signals to activate other components of the immune system.

Natural Killer (NK) cells: NK cells are another type of white blood cell that can recognize and destroy cancer cells without prior exposure. They play an important role in the early stages of immune responses against tumors.

Antigen-Presenting Cells (APCs): These cells, such as dendritic cells, macrophages, and B cells, capture and present antigens (pieces of foreign substances) to T cells. This process helps activate T cells and initiate an immune response against cancer cells.

Cytokines: These are signaling proteins that play a vital role in cell communication during immune responses. They can stimulate or inhibit the immune system, and some cytokines are used in cancer immunotherapy to enhance anti-tumor immunity.

Antibodies: B cells produce antibodies that can recognize and neutralize cancer cells. Antibodies can also combine with other components of the immune system to destroy cancer cells.

Mitochondrial modulation of anti-tumor immune responses

Metabolic reprogramming: T cells, a vital component of the immune system, undergo metabolic reprogramming upon activation. Mitochondria play a fundamental role in this process by facilitating modification in cellular metabolism. Activated T cells switch from oxidative phosphorylation to glycolysis, an alteration known as the "Warburg effect." This metabolic reprogramming supports the rapid energy demands of activated T cells and improves their effector functions. In the context of anti-tumor immunity, efficient metabolic adaptation is important for T cells to support an effective response against cancer cells.

Mitochondrial ROS (Reactive Oxygen Species): Mitochondria are a major source of reactive oxygen species, which are signaling molecules involved in various cellular processes, including immune responses. Moderate levels of mitochondrial ROS are necessary for normal immune function, but excessive ROS could be damaging. A controlled production of ROS in T cells can contribute to their activation and effector functions, supporting in the elimination of cancer cells.

Mitochondrial dynamics: Mitochondria exhibit dynamic processes such as fusion and fission, which influence their morphology and function. These mitochondrial dynamics play a role in regulating T cell activation and differentiation. Modification of mitochondrial dynamics can affect T cell function and impact anti-tumor immune responses.

Mitochondrial DNA (mtDNA) release: Mitochondria contain their own DNA (mtDNA), and under certain conditions, mtDNA can be released into the cytoplasm or extracellular space. This release can generate innate immune responses through the activation of various signaling pathways. In the context of cancer, mtDNA release may influence the immune response against tumor cells.

Apoptosis and cell death: Mitochondria are vital to the fundamental pathway of apoptosis, a programmed cell death process. Tumor cells often develop mechanisms to avoid apoptosis, allowing them to survive and proliferate. Strategies that target mitochondria to cause apoptosis in cancer cells can improve the effectiveness of anti-tumor immune responses.

Regulation of anti-tumor immunity

Immune checkpoints: Immune checkpoints are molecules on the surface of immune cells that regulate the intensity and duration of immune responses. Checkpoint inhibitors are a class of immunotherapy drugs that block these inhibitory signals, allowing to improve the immune system a stronger response against cancer. Examples include programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors.

Tumor antigens: Tumor cells express antigens (proteins) that can be recognized by the immune system. However, some tumors may decrease or alter the expression of these antigens to prevent immune detection. Cancer vaccines and adoptive T cell therapies aim to improve the immune system's recognition of tumor antigens, increasing the anti-tumor immune response.

Tumor Microenvironment (TME): The TME consists of various cell types, including immune cells, fibroblasts, and blood vessels, as well as the extracellular matrix. The TME can influence the behavior of immune cells. Some tumors create an immunosuppressive microenvironment that delays effective anti-tumor immunity. Modulating the TME is a target for therapeutic interventions to increase immune responses against cancer.

Cytokines: Cytokines are signaling molecules that mediate communication between immune cells. Some cytokines, such as Interleukin-2 (IL-2) and interferons, can stimulate the immune system and increase anti-tumor responses. Also, other cytokines may contribute to an immunosuppressive microenvironment.

Adaptive immune resistance: Tumors can adapt to immune pressure by developing mechanisms to resist immune attacks. This adaptive immune resistance may involve alterations in antigen presentation, mutations that reduce immunogenicity, or the stimulation of inhibitory pathways. Understanding and overcoming these adaptive resistance mechanisms are vital for the success of anti-tumor immune therapies.

Conclusion

Understanding the specific role of mitochondria in the regulation of anti-tumor immunity is an evolving area of research. Employing mitochondrial function or targeting specific mitochondrial components may offer different therapeutic strategies to increase the anti-tumor activity of immune cells. However, it's vital to carefully balance interventions to avoid potential side effects on normal cellular functions. Ongoing research is focused on destroying the molecular mechanisms underlying the interaction between mitochondria and the immune system to develop targeted and effective cancer immunotherapies.