Enhancing NK Cell Activity Against Cancer

Natural Killer (NK) Cells: The Immune System's Frontline Warriors Against Cancer(PMC)

Natural Killer (NK) cells are a vital component of our innate immune system, acting as the body's first line of defense against cancerous and virally infected cells. Unlike other immune cells, NK cells can recognize and eliminate abnormal cells without prior sensitization, making them crucial in early tumor surveillance and control .(PMC)

Natural Killer (NK) cells are a special kind of white blood cell that belong to a group called lymphocytes, which help defend your body. They make up about 5–15% of your lymphocytes in the bloodstream (source). Unlike other immune cells like T cells and B cells, which need to “learn” what to attack, NK cells are part of your body’s fast-acting, built-in defense system. They can quickly recognize and attack virus-infected or cancerous cells—even if your body has never seen them before (source).

NK cells do this using a system of “on” and “off” switches on their surface that help them distinguish between healthy cells and those that are dangerous (source). When NK cells identify a problem, they release powerful proteins, such as perforin and granzymes, that puncture the target cells and cause their death. They also release interferon-gamma (IFN-γ), a chemical messenger that helps coordinate a more potent immune attack (source).

Together, these abilities make NK cells an essential first line of defense in protecting your body from infections and cancer.

The Role of NK Cells in Cancer Defense

NK cells possess the unique ability to detect stressed or transformed cells, such as tumor cells, and induce their death through cytotoxic mechanisms. Their activity is regulated by a balance of activating and inhibitory receptors, enabling them to distinguish between healthy and abnormal cells. In cancer patients, NK cell function can be compromised, resulting in decreased surveillance and increased tumor progression.(PMC, PMC)

Lifestyle Factors Enhancing NK Cell Activity

Physical Exercise

Engaging in regular physical activity has been shown to boost NK cell activity. Both acute and chronic exercise can increase the number and cytotoxicity of NK cells, enhancing the body's ability to combat tumor cells. Studies suggest that exercise has a positive influence on the tumor microenvironment, which supports better outcomes for cancer patients.[i] [ii] [iii] This impact is so essential I encourage each of my clients to spend 30 minutes each day in a HIIT (High-Intensity Interval Training) exercise program or significant physical activity to get the heart rate into a fat-burning zone. Download your free HIIT for Cancer Guide.

Foods and NK Cells

Natural killer (NK) cells play a crucial role in immune defense, targeting virus-infected and cancerous cells. Nutrition significantly influences NK cell function, with various macronutrients and dietary patterns shaping their activity. Studies indicate that macronutrients like carbohydrates, fats, and proteins provide essential metabolic support for NK cells. For instance, research highlights that carbohydrates fuel NK cell metabolism, ensuring their cytotoxic function.[iv] Meanwhile, high-fat diets can impair NK cell activity, potentially reducing their ability to combat malignancies.[v] On the other hand, proteins play a crucial role in educating NK cells, thereby influencing their ability to distinguish between healthy and abnormal cells.[vi]

Dietary patterns such as fasting and ketogenic diets also impact NK cell function. Fasting has been shown to enhance NK cell-mediated anti-tumor immunity, redistributing NK cells to the bone marrow and priming them for improved function.[vii] Similarly, ketogenic diets can rewire immune responses, increasing NK cell activity and adaptive immunity.[viii] These findings suggest that dietary interventions could be strategically used to optimize immune function and potentially improve cancer treatment outcomes.

Carbohydrates play a vital role in fueling natural killer (NK) cells, which are essential for immune defense against infections and cancer. NK cells rely on glucose metabolism to sustain their cytotoxic activity and energy demands. Studies indicate that glycolysis, the process of breaking down glucose, is crucial for the activation and function of NK cells. When NK cells encounter infected or malignant cells, they increase their glucose uptake to support the production of cytotoxic molecules, such as granzyme B and perforin, which help eliminate these harmful cells.[ix]

However, excessive carbohydrate intake, particularly in the form of refined sugars, may negatively impact NK cell function. Research suggests that high glucose levels can impair NK cell cytotoxicity, reducing their ability to target and destroy abnormal cells.[x] Additionally, metabolic disorders such as diabetes have been linked to weakened NK cell responses, potentially increasing susceptibility to infections and cancer.[xi] On the other hand, controlled carbohydrate consumption, especially from complex carbohydrates found in whole grains and vegetables, can support NK cell metabolism without causing detrimental effects.

Ginseng

Ginseng and its active component, ginsenoside Rg-1, have been shown to enhance NK cell activity, contributing to improved immune responses .(PMC)

Garlic

Garlic has immunomodulatory effects, including increased natural killer (NK) cell activity and enhanced production of T and B lymphocytes, which support overall immune function.(PMC)

Smoking Nicotine and NK Cells

Smoking and nicotine exposure have been shown to impair natural killer (NK) cell function significantly, weakening the body's ability to combat infections and cancer. Research indicates that nicotine suppresses NK cell cytotoxicity by interfering with the nicotinic acetylcholine receptor β2, reducing their ability to eliminate tumor cells.[xii] Additionally, cigarette smoke exposure inhibits the release of NK cell cytokines, particularly IFN-γ and TNF-α, which are crucial for immune defense.[xiii] Studies also suggest that smoking alters NK cell responsiveness, leading to an increased risk of metastasis in lung cancer models.

Stress and NK Cells

Stress and meditation have profound effects on natural killer (NK) cell activity, influencing immune function and overall health. Research indicates that acute psychological stress can initially boost NK cell mobilization; however, prolonged stress leads to suppressed NK cell cytotoxicity, thereby increasing susceptibility to infections and cancer.[xiv] Stress signals activate NK cells through interferons and cytokines; however, chronic stress disrupts the immune balance, impairing their ability to target abnormal cells.[xv]

Meditation and NK Cells

On the other hand, meditation has been shown to enhance natural killer (NK) cell function, reduce inflammation, and improve immune surveillance.[xvi] These findings suggest that managing stress through meditation and relaxation techniques may help maintain optimal natural killer (NK) cell activity and support overall immune health.

Nutritional Supplements and Natural Compounds

Iodine, Zinc, and Selenium and NK Cells

Iodine, zinc, and selenium play crucial roles in the function of natural killer (NK) cells, influencing immune responses and cytotoxic activity. Iodine has been studied for its potential to enhance NK cell-mediated immunotherapy.  Zinc is essential for NK cell cytotoxicity, with research showing that short-term zinc supplementation enhances NK cell functionality and immune defense.[xvii] Selenium contributes to NK cell activation and immune modulation, with selenium nanoparticles demonstrating the ability to boost NK cell-mediated anticancer effects. [xviii] These findings suggest that adequate intake of these micronutrients may support NK cell activity and overall immune health.

Assess – Don’t Guess

Comprehensive Toxic and Essential Elements Profile tests for iodine, zinc, selenium and several toxic metals.

β-Glucans

β-Glucans, found in sources like mushrooms and yeast, are known to stimulate NK cell activity. They activate immune cells through interactions with specific receptors, enhancing the body's defense mechanisms against tumors.

Beta-glucans, naturally occurring polysaccharides found in fungi, yeast, and grains, have been shown to enhance natural killer (NK) cell function, improving immune responses against infections and cancer. Research indicates that yeast-derived β-glucan can modulate macrophages, leading to increased NK cell activation and cytotoxicity against tumor cells.[xix] Additionally, studies suggest that beta-(1→3)(1→6)-D-glucan enhances NK cell proliferation, particularly in breast cancer models, improving immune surveillance.[xx] Clinical trials have also demonstrated that short-term supplementation with β-glucan increases NK cell numbers, supporting immune recovery in patients undergoing cancer treatment.[xxi] These findings highlight the potential of beta-glucans as immunomodulatory agents that strengthen NK cell-mediated defense mechanisms.

Curcumin and NK Cells

Curcumin, a bioactive compound derived from turmeric, has been shown to modulate natural killer (NK) cell activity, influencing immune responses against cancer and infections. Research suggests that curcumin enhances NK cell-induced apoptosis in pancreatic cancer cells, improving immune surveillance.[xxii] Additionally, studies indicate that curcumin can counteract immunosuppressive signals from cancer cells, restoring NK cell functionality.[xxiii] These findings highlight curcumin's dual role in NK cell regulation, suggesting potential therapeutic applications in cancer immunotherapy.

EGCG and NK Cells

Epigallocatechin gallate (EGCG), a polyphenol found in green tea, has been shown to modulate natural killer (NK) cell activity, influencing immune responses and cancer defense. Research suggests that EGCG enhances NK cell-mediated cytotoxicity, improving their ability to target tumor cells. Additionally, EGCG has been found to suppress immunosuppressive signals in the tumor microenvironment, allowing NK cells to function more effectively. Studies also indicate that EGCG can regulate metabolic pathways, including glucose uptake and fatty acid metabolism, which are crucial for NK cell energy production.[xxiv] These findings highlight EGCG's potential as an immunomodulatory agent, suggesting therapeutic applications in cancer treatment and immune health.

Quercetin and NK Cells

Quercetin, a flavonoid found in various fruits and vegetables, has been shown to modulate natural killer (NK) cell activity, influencing immune responses and cancer defense. Research suggests that quercetin enhances NK cell maturation by binding to MYH9, improving immune surveillance and cognitive function in aging models.[xxv] Additionally, studies indicate that quercetin increases tumor cell susceptibility to NK cell-mediated lysis by inducing NKG2D ligands and suppressing heat shock proteins.[xxvi]

Resveratrol and NK Cells

Resveratrol, a polyphenol found in grapes and red wine, has been shown to modulate natural killer (NK) cell activity, influencing immune responses and cancer defense. Research suggests that resveratrol enhances NK cell-mediated cytotoxicity by activating the Akt and mTORC2 pathways, leading to increased expression of c-Myb, a transcription factor crucial for NK cell function.[xxvii] Additionally, studies indicate that resveratrol can induce apoptosis in malignant NK cells by inhibiting the JAK2/STAT3 pathway, reducing tumor cell proliferation.[xxviii] Furthermore, resveratrol has been found to synergistically enhance NK cell activity when combined with interleukin-2 (IL-2), improving immune surveillance and anti-cancer effects.[xxix] These findings highlight resveratrol's potential as an immunomodulatory agent, suggesting therapeutic applications in cancer treatment and immune health.

Conclusion

NK cells play a pivotal role in the body's defense against cancer. Their activity can be influenced by lifestyle choices, including exercise, diet, and stress management. Incorporating specific nutrients and natural compounds, such as ginseng, garlic, and β-glucans, may further enhance NK cell function. By understanding and supporting NK cell activity, we can bolster our innate immune system's ability to combat cancer.

For more information and resources on enhancing your immune health, visit www.prevailovercancer.com.

[i] Valenzuela, P.L., Saco-Ledo, G., Santos-Lozano, A. et al. Exercise Training and Natural Killer Cells in Cancer Survivors: Current Evidence and Research Gaps Based on a Systematic Review and Meta-analysis. Sports Med - Open 8, 36 (2022).

[ii] Andrea Sitlinger, Danielle M. Brander, David B. Bartlett; Impact of exercise on the immune system and outcomes in hematologic malignancies. Blood Adv 2020; 4 (8): 1801–1811.

[iii] Deppe, I., Beller, R., Kiehl, F. et al. The impact of a single HIIT intervention on the mobilization of NK cells and ILCs in adolescents and young adults (AYA) undergoing cancer treatment: an interventional controlled trial. BMC Cancer 25, 689 (2025).

[iv] https://www.cellphysiolbiochem.com/Articles/000776/

[v] https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.711824/full

[vi] https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1087155/full

[vii] https://www.cell.com/immunity/abstract/S1074-7613(24)00275-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761324002759%3Fshowall%3Dtrue

[viii] https://jamanetwork.com/journals/jama/article-abstract/2815354

[ix] Choi, C., Finlay, D.K. Optimising NK cell metabolism to increase the efficacy of cancer immunotherapy. Stem Cell Res Ther 12, 320 (2021). https://doi.org/10.1186/s13287-021-02377-8

[x] https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01989/full

[xi] Blunt MD. NK Cells in Health and Disease. Biomedicines. 2025; 13(6):1312. https://doi.org/10.3390/biomedicines13061312

[xii] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057495

[xiii] https://academic.oup.com/jleukbio/article-abstract/83/3/774/6975620?redirectedFrom=fulltext

[xiv] Schedlowski, M., Jacobs, R., Stratmann, G. et al. Changes of natural killer cells during acute psychological stress. J Clin Immunol 13, 119–126 (1993). https://doi.org/10.1007/BF00919268

[xv] Eric O. Long, Sumati Rajagopalan; Stress Signals Activate Natural Killer Cells . J Exp Med 2 December 2002; 196 (11): 1399–1402. doi: https://doi.org/10.1084/jem.20021747

[xvi] Nicole C. Guilz, Yong-Oon Ahn, Hijab Fatima, Luis Alberto Pedroza, Seungmae Seo, Rajesh Kumar Soni, Ning Wang, Dieter Egli, Emily M. Mace; Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis. J Immunol 1 July 2024; 213 (1): 40–51. https://doi.org/10.4049/jimmunol.2300843

[xvii] Amling, L., Rink, L. & Bennstein, S.B. Short-term oral zinc supplementation enhances Natural Killer cell functionality and decreases circulating Innate Lymphoid Cell counts and frequencies in healthy young adults. J Transl Med 23, 333 (2025). https://doi.org/10.1186/s12967-025-06259-y

[xviii] https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.956181/full

[xix] Zhichao Zhu, Liuyang He, Yu Bai, Lei Xia, Xiao Sun, Chunjian Qi, Yeast β-glucan modulates macrophages and improves antitumor NK-cell responses in cancer, Clinical and Experimental Immunology, Volume 214, Issue 1, October 2023, Pages 50–60, https://doi.org/10.1093/cei/uxad080

[xx] Boulifa, A., Raftery, M.J., Franzén, A.S. et al. Role of beta-(1→3)(1→6)-D-glucan derived from yeast on natural killer (NK) cells and breast cancer cell lines in 2D and 3D cultures. BMC Cancer 24, 339 (2024). https://doi.org/10.1186/s12885-024-11979-3

[xxi] https://sciencepublishinggroup.com/article/10.11648/j.ijcems.20160202.12

[xxii] Fiala M. Curcumin and Omega-3 Fatty Acids Enhance NK Cell-Induced Apoptosis of Pancreatic Cancer Cells but Curcumin Inhibits Interferon-γ Production: Benefits of Omega-3 with Curcumin against Cancer. Molecules. 2015; 20(2):3020-3026. https://doi.org/10.3390/molecules20023020

[xxiii] Goleij, P., Rezaee, A., Lam, H.Y. et al. From bench to bedside: exploring curcumin-driven signaling pathways in immune cells for cancer management. Inflammopharmacol (2025). https://doi.org/10.1007/s10787-025-01739-5

[xxiv] https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1331641/full

[xxv] Su, T., Shen, H., He, M. et al. Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice. Immun Ageing 21, 29 (2024). https://doi.org/10.1186/s12979-024-00436-1

[xxvi] Bae, Jae-Ho* †; Kim, Joo-Young*; Kim, Mi-Ju* †; Chang, Sung-Ho‡; Park, You-Soo§; Son, Cheol-Hun§; Park, Soo-Jung∥; Chung, Joo-Seop¶; Lee, Eun-Yup♯; Kim, Sun-Hee* †; Kang, Chi-Dug*. Quercetin Enhances Susceptibility to NK Cell-mediated Lysis of Tumor Cells Through Induction of NKG2D Ligands and Suppression of HSP70. Journal of Immunotherapy 33(4):p 391-401, May 2010. | DOI: 10.1097/CJI.0b013e3181d32f22 https://journals.lww.com/immunotherapy-journal/Abstract/2010/05000/Quercetin_Enhances_Susceptibility_to_NK.6.aspx

[xxvii] Lee Y-J, Kim J. Resveratrol Activates Natural Killer Cells through Akt- and mTORC2-Mediated c-Myb Upregulation. International Journal of Molecular Sciences. 2020; 21(24):9575. https://doi.org/10.3390/ijms21249575

[xxviii] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055183

[xxix] Yoojin Lee, Heewook Shin, Jongsun Kim; In vivo Anti-Cancer Effects of Resveratrol Mediated by NK Cell Activation. J Innate Immun 24 March 2021; 13 (2): 94–106. https://doi.org/10.1159/000510315