Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type, has often an aggressive course and is poorly responsive to current therapeutic approaches, so that 5-year survival rates for patients diagnosed with advanced disease is lower than 50%. The Epidermal Growth Factor Receptor (EGFR) has emerged as an established oncogene in HNSCC. Indeed, although HNSCCs are a heterogeneous group of cancers which differ for histological, molecular and clinical features, EGFR is overexpressed or mutated in a percentage of cases up to about 90%. Moreover, aberrant expression of the other members of the ErbB receptor family, ErbB2, ErbB3 and ErbB4, has also been reported in variable proportions of HNSCCs. Therefore, an increased expression/activity of one or multiple ErbB receptors is found in the vast majority of patients with HNSCC. While aberrant ErbB signaling has long been known to play a critical role in tumor growth, angiogenesis, invasion, metastatization and resistance to therapy, more recent evidence has revealed its impact on other features of cancer cells' biology, such as the ability to evade antitumor immunity. In this paper we will review recent findings on how ErbB receptors expression and activity, including that associated with non-canonical signaling mechanisms, impacts on prognosis and therapy of HNSCC.

Polyphenols affect the humoral response in cancer, infectious and allergic diseases and autoimmunity by modulating the activity of TH1 and TH2 cells.

Polyphenols are a wide class of natural substances, pleiotropic molecules capable of modulating several processes, involved in the humoral and cellular immune response. The activation, differentiation of B cells, and production of antibodies to protein antigens by plasma cells depend on T helper (TH) CD4+ cells and secreted cytokines. Cancer, infectious, allergic, and autoimmune diseases are characterized by an imbalance of TH1/TH2 immunity and abnormal activation of the humoral response. Accordingly, polyphenols modulate the TH1/TH2 ratio, the secretion of multiple cytokines, the levels of antibodies, and therefore could contribute to recovering the state of health in these diseases. In this review, we summarize the current knowledge on the effects of polyphenols in modulating the humoral response in cancer, infectious and allergic diseases and in autoimmunity by affecting the activity of TH1 and TH2 cells.

Targeting the tumor immune microenvironment with "nutraceuticals": From bench to clinical trials.

The occurrence of immune effector cells in the tissue microenvironment during neoplastic progression is critical in determining tumor growth outcomes. On the other hand, tumors may also avoid immune system-mediated elimination by recruiting immunosuppressive leukocytes and soluble factors, which coordinate a tumor microenvironment that counteracts the efficiency of the antitumor immune response. Checkpoint inhibitor therapy results have indicated a way forward via activation of the immune system against cancer. Widespread evidence has shown that different compounds in foods, when administered as purified substances, can act as immunomodulators in humans and animals. Although there is no universally accepted definition of nutraceuticals, the term identifies a wide category of natural compounds that may impact health and disease statuses and includes purified substances from natural sources, plant extracts, dietary supplements, vitamins, phytonutrients, and various products with combinations of functional ingredients. In this review, we summarize the current knowledge on the immunomodulatory effects of nutraceuticals with a special focus on the cancer microenvironment, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of nutraceuticals for envisioning future therapies employing nutraceuticals as chemoadjuvants.