"Altered 'NK Cells' Due to Stress Weaken Cancer Immunity"

A recent study has found that 'NK cells', which have been altered by chronic environmental stress and unhealthy lifestyle habits, can undermine cancer immunity.

NK cells are innate immune cells that are originally responsible for directly attacking and destroying virus-infected cells or cancer cells. However, the research revealed that when these cells become altered, they actually contribute to the development of so-called 'cold tumors', which have weak immune responses.

Cold tumors refer to so-called 'cold' tumors where immune cells either do not gather around the tumor or fail to infiltrate it, resulting in a poor response to immunotherapy drugs.

Professor Moon Yoo-seok. National Research Foundation of Korea

The National Research Foundation of Korea announced on June 9 that a research team led by Professor Mooyuseok Moon at Pusan National University has molecularly identified the impact of altered NK cells (characterized by energy exhaustion and maladaptive changes) on the failure to eliminate tumors when these cells predominantly infiltrate and accumulate in cancer tissue.

Cold tumors, which are solid tumors with extremely low immune responsiveness such as breast, prostate, and ovarian cancers, are the most common tumors among Korean men and women. Environmental factors and lifestyle habits have previously been cited as causes of the poor (altered) immune response in these tumors. However, while these factors have been hypothesized, the biological mechanisms had not been elucidated.

It is widely known that tens of thousands of environmental endocrine-disrupting hormones, which enter the human body through air, water, and food, pose health risks. However, a direct causal relationship (in terms of disease progression) between these hormones and immune cells within actual tumors had not been clearly confirmed.

In this regard, the research team analyzed tumor immune responses triggered by chronic environmental stress receptor stimulation, such as endocrine hormone disruption, and discovered that a cancer cell-derived factor (Gdf15) promotes the signaling of the environmental stress receptor, aryl hydrocarbon receptor (AhR), thereby reconstructing the tumor immune microenvironment.

The aryl hydrocarbon receptor is a receptor that binds to environmental hormones such as dioxin, transmitting signals inside the cell, and plays a vital role in regulating immune responses.

During their analysis, the team also confirmed that when NK cells infiltrating the tumor are continuously stimulated by the aryl hydrocarbon receptor, they initially display anti-cancer activity but, over time, undergo a maladaptive transformation with increased energy exhaustion and genetic damage.

Furthermore, the study demonstrated through clinical data and animal models that when these altered 'dysfunctional NK cells' predominantly accumulate within cancer tissue, the immune system fails to eliminate the cancer cells, and these cells may actually serve as indicators for predicting tumor recurrence and progression.

Professor Moon stated, "Our research has identified at the molecular level that chronic environmental stress and unhealthy lifestyle habits, rather than genetic factors, can also lead to the development of low-immune-response 'cold tumors' in ovarian, breast, and prostate cancers, thereby weakening cancer immunity. This finding highlights the limitations of simply increasing the quantity of NK cells as a treatment, and suggests that the next generation of immunotherapy drugs should focus on preventing and restoring NK cell function in response to environmental stress."

This research was supported by the Regional University Distinguished Scientist Program and the Doctoral/Post-Doctoral Researcher Growth-Type Joint Research Program, both promoted by the Ministry of Science and ICT and the National Research Foundation of Korea. The findings were published online on June 5 in the international academic journal Signal Transduction and Targeted Therapy, which specializes in biochemistry and molecular biology.

This content was produced with the assistance of AI translation services.