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New Strategy for Head and Neck Squamous Cell Carcinoma Treatment via Immune Regulation

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Background: Chronic inflammation may promote cancer, and reducing inflammation may improve survival from cancer. The inflammatory response occurs through increased T-helper 1 (Th1) immunity and decreased T-helper 2 (Th2) immunity. Tumor-associated macrophage (TAM) promote cancer progression is common population for Th2 dominant in the tumor microenvironment. Moreover, cancer-associated fibroblast (CAF) and regulatory T cell (Treg) were also the Th2 dominant subsets has been reported in many cancer types. Thus, we try to summarize the correlation of immune cell in head and neck squamous cell carcinoma (HNSCC) progression.

Methods: We review the role of immune cells in the tumor microenvironment and the recent immunotherapy in HNSCC.

Results: Numerous signaling networks connect tumor cells with inflammatory cells. However, the mechanism underlying recruitment and infiltration of inflammatory cells into the tumor stroma remains unclear. Tumor cells may be escape from the immune system to avoid eliminated by immune cells. To a tumor cell, an infiltrating immune cell might be a " friend " that skews it toward the Th2 dominant and promote tumor growth, or a " foe " that skews it toward the Th1 dominant and enhance tumor regression.

Conclusions: Breaking the crosstalk between tumor cells and infiltrating cells has potential to improve the clinical outcomes of patients with cancer.

اثرات Th1/Th2 بر پیشرفت تومور.  سلول های T ساده به دنبال تحریک توسط عوامل مختلف به سلول های Th1 یا سلول های Th2 تبدیل می شوند.  در ایمنی Th1، سلول ها سیتوکین های پیش التهابی مانند اینترلوکین-2 (IL2)، اینترفرون-گاما (IFN-γ) و فاکتور نکروز تومور بتا (TNF-β) تولید می کنند.  در ایمنی Th2، سلول ها سیتوکین های ضد التهابی مانند IL-4، IL-5، IL-6، IL-10 و IL-13 تولید می کنند.  در شرایط عادی، ایمنی Th1 و ایمنی Th2 به تعادل نزدیک می شوند.  اما وجود سلول های تومور این تعادل را بر هم می زند.  این اتفاق باعث افزایش ایمنی Th2 و کاهش ایمنی Th1 به دلیل کاهش ایمنی تطبیقی ​​شد.  این در نهایت منجر به پیشرفت تومور می شود.  با این حال، اگر ایمنی Th1 غالب شود، این تحریک ایمنی می تواند منجر به پسرفت تومور شود. 

Effects of Th1/Th2 on tumor progression. Naive T cells become Th1 cells or Th2 cells, following the stimulation by different factors. In Th1 immunity, cells produce pro-inflammatory cytokines, such as interleukin-2 (IL2), interferon-gamma (IFN-γ), and tumor necrosis factor-beta (TNF-β). In Th2 immunity, cells produce antiinflammatory cytokines, such as IL-4, IL-5, IL-6, IL-10, and IL-13. In normal circumstances, Th1 immunity and Th2 immunity approach a balance. But, the presence of tumor cells disrupts this balance. This occuring increased Th2 immunity and decreased Th1 immunity, because of down-regulation of adaptive immunity. This eventually leads to tumor progression. However, if Th1 immunity becomes predominant, this stimulation of immunity can lead to tumor regression.

Factors that May Balance the Immune System (Lower Th2)

Top 10

  1. Sun/UVB light [1] – UVB decreases IFNy in Th1 dominance but increases it in Th2 dominance. So it’s balancing. It also decreases IgE responses. UVA in the sun also decreases Th2 dominance [2].
  2. Probiotics… Decreases Th2: L Reuteri [3] (probiotic), L. Plantarum [4] (probiotic), L. salivarius [4] (probiotic), L. lactis [4] (probiotic)… Increases Th1: S Boulardii? [5], L. Sporogenes, L Acidophilus [6], L casei [7], Lactobacillus rhamnosus GG [8], Lactobacillus paracasei [9], Lactobacillus salivarius [9], B Longum [10], L Brevis [11], L fermentum [12].
  3. NAC/Glutathione sufficiency decreases Th2 [13] and increases Th1 [14].
  4. Licorice -18/β-glycyrrhetinic acid+LicoA [15, 16]. Glycyrrhizin increases IFNy and decreases the Th2 response [17, 18].
  5. Gynostemma [19]. This is a Th1 immune stimulant and reduces allergies. Gynostemma is recommended also because it’s a powerful mitochondrial enhancer.
  6. Ginger or juice the root [20, 21]. Recommended because it has anecdotal support in addition to the research, but also because you can get it everywhere, it has a long history of use and for its multitude of other benefits.
  7. Reishi [22]
  8. Tinospora [23]. This has a clinical trial backing it, with some anecdotal support.
  9. Quercetin [24]
  10. Astragalus [25] Decreases Th2 and increases Th1.



Other (Experimental)

The following might lower Th2 but should be avoided because of numerous detrimental health effects: Nicotine [92], Choline deficiency [93], and Zinc deficiency [94].