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3.3 Immune system enhancement The natural substances can act as immune checkpoint and co-inhibitory modulators, some polyphenols decrease the expression of tissue-and tumoural PD-L1 or of CTLA-4 on T cells giving a mechanistic reasoning to combination with nutritional support in patients treated with check point inhibitors, eventually reversing acquired resistance to treatment or decreasing the effective dose for drug administration (193)

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The effect of local postmenopausal production of E2 within the liver is likely to be relatively small compared to the effect of systemic E2 exposure in the premenopausal state (17)