Focus on immune checkpoint PD-1/PD-L1 pathway: New advances of polyphenol phytochemicals in tumor immunotherapy

Liu, Kunjing; Sun, Qi; Liu, Qi; Li, Huayao; Zhang, Wenfeng; Sun, Changgang

doi:10.1016/j.biopha.2022.113618

Cited by 28 publications

(17 citation statements)

References 224 publications

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“…Combined and reduced wordiness: Apigenin and its metabolite luteolin inhibit IFN-γ-induced PD-L1 expression in human and mouse breast cancer cells by suppressing STAT1 activation [ 135 ]. This effect extends to melanoma, as apigenin and curcumin treatment significantly suppresses tumor growth by inhibiting PD-L1 expression in melanoma cells [ 136 , 137 ]. Anthocyanin and its metabolites significantly inhibit both PD-1 and PD-L1 expression, promoting an immune response and suppressing colon cancer progression [ 138 , 139 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

Golonko,

Pienkowski,

Swislocka

et al. 2024

Cell Death Dis

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Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering substantial advantages when compared to chemotherapy or radiotherapy. However, in the context of immunotherapy, there is the potential for the immune system to either support or hinder the administered treatment. This review encompasses recent and pivotal studies that assess the influence of dietary elements, including vitamins, fatty acids, nutrients, small dietary molecules, dietary patterns, and caloric restriction, on the ability to modulate immune responses. Furthermore, the article underscores how these dietary factors have the potential to modify and enhance the effectiveness of anticancer immunotherapy. It emphasizes the necessity for additional research to comprehend the underlying mechanisms for optimizing the efficacy of anticancer therapy and defining dietary strategies that may reduce cancer-related morbidity and mortality. Persistent investigation in this field holds significant promise for improving cancer treatment outcomes and maximizing the benefits of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

Golonko,

Pienkowski,

Swislocka

et al. 2024

Cell Death Dis

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“…Recent research has indicated that EGCG can play an antitumor immunological role by targeting PD-L1 molecule ( 248 ). Evidence suggested that unlike anti-immune checkpoint therapy, which simply obstructs PD-1/PD-L1 interactions, EGCG suppressed JAK/STAT signaling and downstream PD-L1 expression in melanoma cells, thereby reactivating CTLs to inhibit tumor cell growth ( 29 ).…”

Section: Potential In Anti-cancer Immunotherapymentioning

confidence: 99%

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Li,

Cao,

Sun

et al. 2024

Front. Immunol.

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Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.

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“…Given that the PD-1/PD-L1 pathway has an important role in the generation of an immunosuppressive microenvironment in tumors, there has been a significant interest in examining the regulation mechanisms underpinning the expression of the PD-L1 protein [ 43 , 87 , 88 ]. It seems that there exists a complex network of regulatory processes from epigenetic to post-transcriptional mechanisms which not only control the expression level of PD-L1 but also the resistance to the PD-1/PD-L1 blocking therapies.…”

Section: The Aging-associated Signaling Stimulates the Expression Of ...mentioning

confidence: 99%

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases

Salminen

2024

J Mol Med

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The accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance indicates that there is some defect in the function of cytotoxic immune cells, e.g., CD8+ T cells and natural killer (NK) cells. Recent studies have revealed that the expression of programmed death-ligand 1 (PD-L1) protein is abundantly increased in senescent cells. An increase in the amount of PD-L1 protein protects senescent cells from clearance by the PD-1 checkpoint receptor in cytotoxic immune cells. In fact, the activation of the PD-1 receptor suppresses the cytotoxic properties of CD8+ T and NK cells, promoting a state of immunosenescence. The inhibitory PD-1/PD-L1 checkpoint pathway acts in cooperation with immunosuppressive cells; for example, activation of PD-1 receptor can enhance the differentiation of regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), and M2 macrophages, whereas the cytokines secreted by immunosuppressive cells stimulate the expression of the immunosuppressive PD-L1 protein. Interestingly, many signaling pathways known to promote cellular senescence and the aging process are crucial stimulators of the expression of PD-L1 protein, e.g., epigenetic regulation, inflammatory mediators, mTOR-related signaling, cGAS-STING pathway, and AhR signaling. It seems that the inhibitory PD-1/PD-L1 immune checkpoint axis has a crucial role in the accumulation of senescent cells and thus it promotes the aging process in tissues. Thus, the blockade of the PD-1/PD-L1 checkpoint signaling might be a potential anti-aging senolytic therapy. Key messages Senescent cells accumulate within tissues during aging and age-related diseases. Senescent cells are able to escape immune surveillance by cytotoxic immune cells. Expression of programmed death-ligand 1 (PD-L1) markedly increases in senescent cells. Age-related signaling stimulates the expression of PD-L1 protein in senescent cells. Inhibitory PD-1/PD-L1 checkpoint pathway suppresses clearance of senescent cells.

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Focus on immune checkpoint PD-1/PD-L1 pathway: New advances of polyphenol phytochemicals in tumor immunotherapy

Cited by 28 publications

References 224 publications

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases

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