1. Introduction: The Role of Macrophages in Immune Function

Macrophages are large, mononuclear phagocytic cells that play an essential role in both innate and cell-mediated immunity. As an important component of the body's natural defense system, they help identify and eliminate invading microorganisms, remove damaged cells, and participate in immune responses against abnormal cells, including tumor cells.

Macrophage activation is involved in regulating several important immune processes. When activated, macrophages can produce various biologically active substances, including reactive oxygen species (ROS), reactive nitrogen species (RNS), free radicals, and inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α).

TNF-α is an important signaling molecule originally identified for its ability to induce hemorrhagic necrosis in certain tumor models. It is now recognized as a multifunctional cytokine involved in cell differentiation, immune activation, proliferation, inflammation, and cell survival.

Understanding how macrophage activity is regulated is therefore important for investigating immune responses and potential approaches to immune modulation.

2. Millimeter Waves and Macrophage Activation

Research has investigated the potential effects of millimeter waves (MMWs) on macrophage activity and cytokine production.

In one experimental study, cyclophosphamide (CPA) treatment in mice significantly reduced the spontaneous release of TNF-α by peritoneal macrophages. Following millimeter-wave irradiation, TNF-α production returned toward normal levels [26].

These findings suggest that millimeter-wave exposure may influence macrophage function and cytokine regulation under certain experimental conditions.

Other studies have also reported changes in macrophage activity following millimeter-wave exposure [51]. However, the biological mechanisms underlying these responses remain an area of scientific investigation.

Macrophages and Their Relationship with Tumor Cells

Macrophages have a complex relationship with cancer development and progression. Depending on their activation state and the surrounding tumor microenvironment, they may contribute to tumor cell destruction or, alternatively, support tumor growth and metastasis [52,53].

Certain activated macrophages can recognize and interact with abnormal cells through differences in cell-surface composition and signaling molecules.

One molecule of interest is phosphatidylserine (PS), a phospholipid normally located primarily on the inner surface of the cell membrane. During apoptosis, PS can become exposed on the outer surface of the membrane, acting as an important signal for the recognition and clearance of dying cells.

Some experimental research has investigated whether millimeter-wave exposure can influence phosphatidylserine externalization and apoptosis-related processes [54,55].

These observations provide a basis for further research into the interactions between millimeter waves, cell-membrane signaling, apoptosis, and macrophage-mediated immune responses.

Nevertheless, it is important to distinguish laboratory findings from established clinical outcomes. The ability of millimeter waves to selectively destroy tumor cells or provide effective cancer treatment has not been established through sufficient clinical evidence.

3. Millimeter Waves and the Regulation of Drug Resistance

One of the major challenges in cancer treatment is the development of resistance to chemotherapy. When tumor cells become less responsive to anticancer drugs, treatment effectiveness may decrease, making disease management more difficult.

An important molecular pathway associated with chemotherapy resistance is nuclear factor kappa B (NF-κB).

NF-κB is a transcription factor that regulates the expression of numerous genes involved in inflammation, immune responses, cell survival, and apoptosis. Research has shown that certain anticancer drugs can activate NF-κB signaling pathways, potentially increasing the survival of cancer cells under treatment conditions.

Both constitutive and drug-induced NF-κB activation have been associated with mechanisms that protect tumor cells against apoptosis and contribute to chemotherapy resistance [56–58].

Consequently, scientists have investigated whether inhibiting abnormal NF-κB activation could help improve the sensitivity of tumor cells to chemotherapy.

Experimental findings have indicated that suppressing inducible NF-κB activity may reduce certain forms of tumor resistance to anticancer drugs [59,60].

Potential Effects of Millimeter Waves on NF-κB Activity

Previous experimental research has reported that millimeter-wave irradiation can inhibit cyclophosphamide (CPA)-induced NF-κB activation under specific laboratory conditions [61].

This observation has attracted scientific interest because NF-κB signaling is involved in several cellular processes associated with inflammation, apoptosis, and drug resistance.

The findings suggest a possible interaction between millimeter-wave exposure and intracellular signaling pathways. However, the precise mechanisms through which millimeter waves may influence drug-induced NF-κB activation have not yet been fully clarified.

Further studies are needed to determine the reproducibility, biological significance, and potential clinical relevance of these observations.

4. Future Research Perspectives

The relationship between millimeter waves, macrophage activity, and intracellular signaling pathways represents an interesting area of biomedical research.

Several topics deserve further investigation:

• Macrophage regulation: Understanding how millimeter-wave exposure may influence macrophage activation and cytokine production.

• TNF-α expression: Investigating changes in inflammatory signaling and immune-related cytokine responses.

• Cell-membrane signaling: Exploring the relationship between millimeter waves, phosphatidylserine externalization, and apoptosis.

• NF-κB pathways: Examining how millimeter-wave exposure may affect intracellular signaling associated with cell survival and drug resistance.

• Biological safety: Evaluating exposure parameters, tissue responses, potential side effects, and long-term safety.

These research directions may help clarify the biological interactions between millimeter electromagnetic waves and living cells.

5. Conclusion

Macrophages are essential immune cells involved in inflammation, cellular defense, and the recognition and clearance of abnormal cells. Their activity is regulated by multiple signaling molecules and intracellular pathways, including TNF-α and NF-κB.

Experimental studies have suggested that millimeter-wave exposure may influence macrophage cytokine production, apoptosis-related processes, and certain signaling pathways associated with cellular responses to anticancer drugs.

Although these findings provide interesting directions for further investigation, the underlying mechanisms and clinical significance remain to be established.

Continued research into millimeter-wave interactions with immune cells and cellular signaling may contribute to a better understanding of their potential biomedical applications.