Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies

Abstract

In early tumor development, cancer cells develop a plethora of strategies to escape surveillance from the adaptive and innate immune system. Cancer immunotherapies, in particular immune checkpoint inhibitors, are becoming a highly promising cancer therapeutic approach that has remarkable increased progress in combating various cancer types. Unfortunately, their mechanisms of action induce some complications, such as inflammatory reactions and immune-related adverse events. In the management of side effects during anticancer therapy, complementary and integrative therapy approaches are becoming of growing interest. Particularly, mistletoe, Viscum album L. (VA), has a long traditional history of about 100 years as an add-on therapy of cancer treatment in German-speaking countries. Besides antitumoral and quality of life-promoting activities, VA applications reduce side effects of modern conventional anticancer therapies and exert immunomodulatory characteristics. As these properties may provide a good basis for a combination with modern oncological therapies, the biological activities of VA applications and mechanisms involved have to be understood. In this review, the impact of VA compounds on different cellular pathways and immunological reactions in the fight against cancerous cells is discussed.

Viscum album L. homogenizer‐assisted and ultrasound‐assisted extracts as potential sources of bioactive compounds

“…Mistletoe preparations are available in association with conventional cancer treatment to decrease side effects with mild to moderate adverse drug reactions. In cancer medicine, they are associated with conventional treatments such as surgery, radiotherapy, and chemotherapy; patients treated with mistletoe improve their physical and psycho‐sensorial quality of life (Oei, Thronicke, & Schad, 2019).…”

Evaluation of an Expert Guided Integrative Therapy Concept in Patients With Breast or Gynecological Cancer During Systemic Therapy

“…[31][32][33][34] In context of new treatments such as immunomodulation, phytotherapeutics like Viscum album have to be tested in vitro for interactions. 35 Because of the known potential for interactions, every individual CAM treatment plan is checked for interactions with the common systemic cancer therapy at our cancer center. 28 Patients assigned to exercise and nutritional counseling within the ZIGG program were sent to the center of preventive and sports medicine.…”

Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action

“…Furthermore, mistletoe can cause cell cycle arrest (Dela Cruz et al 2015;Kim et al 2017;Melo et al 2018), loss of mitochondrial membrane permeability (MMP) (Mishra et al 2018) and can activate caspases and regulate pro-and anti-apoptotic proteins (Fan et al 2019) (Table 1). The anticancer activity of Viscum species is linked with their immunomodulatory activity (Oei et al 2019), such as the increase of maturation and activation of dendritic cells (Elluru et al 2008;Kim et al 2014a;Steinborn et al 2017), abrogation of tumour-induced immunosuppression of dendritic cells (Steinborn et al 2017), increase of leukocytes, eosinophils, granulocytes (Huber et al 2005(Huber et al , 2011 and lymphocytes (Semiglasov et al 2004), increase of cytokines secretion (Hajto et al 1990;Kovacs 2000;Elluru et al 2008), increase of activity of natural killer cells (Hajto 1986;Tabiasco et al 2002;Braedel-Ruoff 2010;Kim et al 2018), increase of the activities of natural killer cells during surgery (Schink et al 2007) and enhancement of cellular and humoral immune response (Yoon et al 2001;Gardin 2009). Clinical studies were done on patients suffering from cancer diseases such as bladder cancer, breast cancer, colorectal cancer, glioma, lung cancer, melanoma and the results of these studies have been published in many articles.…”