The innate immune system plays a pivotal role in the first line of host defense against infections and is equipped with patterns recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Several classes of PRRS, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) recognize distinct microbial components and directly activate immune cells. TLRs are transmembrane receptors, while NLRs and RLRs are intracellular molecules. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. The innate immune system also influences pathways involved in cancer immunosurveillance. Natural and synthetic agonists of TLRs, NLRs, or RLRs can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment, and are being explored as promising adjuvants in cancer immunotherapies. In this review, we provide a concise overview of TLRs, NLRs, and RLRs: their structure, functions, signaling pathways, and regulation. We also describe various ligands for these receptors and their possible application in treatment of hematopoietic diseases.

Introduction: Location of malignant melanoma lesions depends on environmental, genetic, sociological and demographical factors. Available sources do not provide enough information on such dependencies in various populations. There is no data concerning the role of socio-demographic factors for the population of the Central and Eastern Europe. Aim: The aim of this work was to evaluate the anatomical location of the primary malignant melanoma lesion in correlation to patients’ gender and age. Material and methods: A retrospective analysis of medical documentation of 363 patients has been performed. The patients had been diagnosed with malignant melanoma and were undergoing treatment in the years 2010-2014 in two Polish oncologic hospitals. The subject group consisted of 199 (55%) females and 164 (45%) males. The age varied between 19 - 90 years, with the median of 62 years. Results: In women, the melanoma lesions seem to appear more often in their lower extremities, while in case of men such lesions seem to be more often on their torsos. In both cases, the difference was statistically significant (ppatients. The lesions located on heads and necks were most common in older patients, and the lesions located in lower extremities were most common in younger ones. Conclusion: Differences in location of malignant melanoma lesions may be due to either genetic or environmental reasons. It is often emphasized in literature that correlation between the socio-demographic factors and the process of oncogenesis requires intensive research. In our work, we have tried to fill this gap for the population of Central and Eastern Europe to determine the exact epidemiology of this kind of cancer. This knowledge may be then used for developing cancer prevention methods specific to gender and age.

Myelodysplastic syndromes (MDSs) belong to a group of clonal bone marrow malignancies. In light of the emergence of new molecules, a significant contribution to the understanding of the pathogenesis of the disease is the study of the B-cell CLL/lymphoma 2 (BCL-2) and the programmed cell death receptor 1 (PD-1) protein and its ligands. BCL-2-family proteins are involved in the regulation of the intrinsic apoptosis pathway. Disruptions in their interactions promote the progression and resistance of MDSs. They have become an important target for specific drugs. Bone marrow cytoarchitecture may prove to be a predictor of response to its use. The challenge is the observed resistance to venetoclax, for which the MCL-1 protein may be largely responsible. Molecules with the potential to break the associated resistance include S63845, S64315, chidamide and arsenic trioxide (ATO). Despite promising in vitro studies, the role of PD-1/PD-L1 pathway inhibitors has not yet been established. Knockdown of the PD-L1 gene in preclinical studies was associated with increased levels of BCL-2 and MCL-1 in lymphocytes T, which could increase their survival and promote tumor apoptosis. A trial (NCT03969446) is currently underway to combine inhibitors from both groups.

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

Treatment Outcome and Prognostic Factors for Malignant Skin Melanoma Treated with Radical Surgery Malignant skin melanoma;prognostic factors;radical surgery;distant metastases;tumor diameter; Aim: To assess the treatment outcome in patients with malignant skin melanoma and prognostic factors for distant metastases (DM), disease-free survival (DFS) and overall survival (OS). Materials and Methods: A retrospective analysis was conducted on 113 patients with malignant skin melanoma (60 females, 53 males, average age-55 years) who were treated surgically. Primary treatment consisted of local excision. In 12 cases, it was accompanied by lymph node excision. In 93 (82%) cases, radicalization was necessary, which was either local only (19 cases) or accompanied by lymph node surgery/biopsy (74 cases). Possible prognostic factors such as Clark's stage and Breslow's depth of invasion, ulceration, average tumor dimensions, lymph nodes metastases (pN+), gender, tumor location and primary excision margins were considered. Results: In 51 (45%) cases, treatment failure occurred. The 5-year DM rate was 47%, the 5-year DFS was 38%, and the 5-year OS was 56%. In the univariate analysis, the important factors with respect to at least one endpoint included Clark's stage, Breslow's depth of invasion, ulceration, average tumor dimensions, lymph nodes metastases, gender and primary tumor localization. The presence of metastasic nodes was the most important prognostic factor, with a 5-year DM rates of 30% for pN(-) and 76% for pN(+) and a 5-year DFS and OS of 56% and 76% for pN(-) and 13% and 24% for pN(+), respectively. The average tumor dimension was independently significant for DFS and OS, with 5-year rates of 69% and 80% for ${\leq}1cm$, 28% and 53% for 1-2 cm, and 18% and 30% for >2 cm, respectively. Tumor location was also significant for DM and OS, with 5-year rates of 69% vs 33% and 41% vs 66% for trunk vs other locations, respectively. Conclusions: The natural course of a malignant skin melanoma treated radically is disadvantageous, with unsuccessful outcome in nearly half of the cases. Common clinical factors, such as Clark's tumor stage, Breslow's depth of invasion and the presence of metastatic nodes, have high prognostic significance. The size and location of the primary lesion may be considered independent prognostic factors. The most important negative prognostic factor is the presence of metastatic regional lymph nodes. Only one quarter of patients with metastases in lymph nodes survive 5 years from primary surgery.