The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids. To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB. Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome. Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules. It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared. This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology. We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival. A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy.

Abstract.Immunotherapy is a promising therapeutic option for patients with non-small cell lung cancer (NSCLC) who do not qualify for surgery. In patients with advanced NSCLC, systemic immune suppression is frequently observed, therefore, researchers are investigating the tumor microenvironment for less invasive and more effective methods of treating lung cancer. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are potent suppressors of tumor immunity; therefore, this population may significantly impede the application of immunotherapy to treat cancer. The present study evaluated the distribution of Mo-MDSCs and monocytes/macrophages in the peripheral blood, lymph nodes and tumor tissue of patients with NSCLC. Furthermore, the profiles of cytokines produced by these cell populations, including interleukin (IL)-1β, IL-12/23p40, IL-10, transforming growth factor-β (TGF-β) and tumor necrosis factor (TNF), were compared. The cell populations and the expression of cytokines were assessed by flow cytometry after 4 h in culture with mitogens and Brefeldin A. Mo-MDSCs were more numerous than monocytes/macrophages in all tissues and their prevalence was highest in the peripheral blood; they expressed higher levels of TGF-β than monocytes/macrophages in all

The present study was carried out to assess the percentage of T helper 17 (Th17) lymphocytes in blood and tissue and IL-17A serum concentrations in patients with epithelial ovarian tumors. Two isoforms, IL-17A and IL-17F, as well as IL-21 and IL-22, were simultaneously investigated. The study group consisted of 60 women affected by epithelial ovarian tumors (benign, borderline and malignant) and 20 women without ovarian pathology as a control group. The evaluation of the percentage of Th17 cells secreting IL-17A, IL-17F, IL-21 and IL-22 in peripheral blood and tumor tissues was performed using flow cytometry applying a Th17 cytokine staining panel. The blood serum concentration of IL-17A was determined using ELISA. We found no statistically significant differences in the subpopulations of Th17 lymphocytes, either in peripheral blood or in ovarian tissues, following comparison of the women with and without ovarian pathology. Negative correlations were found between the percentage of CD4+/IL-21+ (rs=0.8, p=0.02) and CD4+/IL-17+ (rs=-0.78, p=0.03) in the tissue and IL-17A in blood serum in the group of patients with borderline ovarian tumors. A negative correlation was also found between IL-17A and the percentage of CD4+/IL-21+ in peripheral blood (rs=‑0.48, p=0.03) in the group of patients with ovarian cancer. The increased percentage of Th17 cells in tissue was not correlated with the overall survival of the ovarian cancer patients. In conclusion, we showed that more Th17 cells secreted IL-17A and IL-21 in the tissue of borderline ovarian tumors and less IL-17A in serum. We also observed that in peripheral blood of the patients with ovarian cancer, there was a higher percentage of Th17 lymphocytes and a lower concentration of IL-17A in serum indicating a negative correlation. An increased percentage of Th17 cells in ovarian tissue does not influence the time of survival of patients with ovarian cancer.

IntroductionNatural killer T (NKT) cells are involved in the antitumor response by direct cytotoxicity and indirectly through activation of effector cells. Recent studies have shown a relationship between the number and function of NKT cells and clinical outcomes. NKT cells seem to represent a promising tool for immunotherapy of cancer.The aim of the studyThe aim of the study was to evaluate the distribution of NKT cells in peripheral blood, lymph nodes and tumor tissue of non-small cell lung cancer (NSCLC) patients, as well as development of the most efficient set of cytokines stimulating differentiation of NKT cells.Material and methodsWe evaluated the percentage of iNKT+CD3+ cells in the tissues collected from patients with NSCLC. For the generation of NKT cells, we cultured cells isolated from the blood of 20 healthy donors and from the tissues of 4 NSCLC patients. Cells were stimulated with α-GalCer in combinations with cytokines.ResultsWe noted significant differences in the percentages of NKT cells in the patients’ tissues. The highest percentage of these cells was observed in the tumor tissue and the lowest in the lymph nodes. In vitro, in healthy donors all α-GalCer-cytokine combinations were effective in stimulation of NKT cells’ proliferation. NKT cells’ proliferation was the most efficiently stimulated by α-GalCer+IL-2+IL-7 and α-GalCer+IL-2+IFN-γ.ConclusionsOur results suggest that in the course of NSCLC, NKT cells migrate to the primary tumor and accumulate therein. All tested combinations of α-GalCer and cytokines were capable of generation of NKT cells in vitro.

Th17 cells are newly described population of lymphoctyes, that recruits neutrophils to the site of inflammation and activate inflammatory phenotype of various tissues. They also play a pivotal role in autoimmune diseases and cancers. These cells secrete mainly different isoforms of IL-17, but also IL-21 and IL-22. Rheumatoid arthritis and juvenile idiopathic arthritis are the most common autoimmune joints’ inflammatory disease, affecting respectively adults and children. For a long time the immunopathogenesis of autoimmune diseases has been associated with Th1 lymphocytes. This hypothesis has changed after the discovery of Th17 cells, which are thought to be key mediators of autoimmune arthritides