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Summary. Natural killer (NK) cells play an important role in immune surveillance against malignant diseases. Considering the lymphoid origin of malignant lymphomas, as well as scarce data concerning NK-cell function in these neoplasms, we evaluated NK-cell activity in 49 patients with nonHodgkin's lymphomas (NHL) and 47 patients with Hodgkin's disease (HD), prior to therapy. Using the recommended International Working Formulation and the Ann Arbor staging system for classification of lymphomas we found, by the LDH release cytotoxicity assay, that decreased NK-cell activity (P < 0·05) in NHL patients was essentially related to unfavourable histology (13 indolent lymphomas, 25 intermediate and 11 very aggressive lymphomas were included), but that within these categories clinical stage of the disease also contributed to the degree of NK-cell dysfunction. In contrast, in HD, NK-cell activity was persistently decreased (P < 0·05), compared to controls, irrespective of histological type and clinical stage. It is of interest also that the most profound NK-cell dysfunction that is present and persistent from the onset of HD, and which appears in very aggressive NHL was associated with the phenomenon of increased spontaneous lactate acid dehydrogenase (LDH) release activity from the separated PBMC of these patients. The difference in the level of NK-cell impairment between patients with various histological grades of malignancy in NHL and HD suggests different initial participation of innate immune reactions in these diseases.

Natural killer (NK) cells play a role in the innate and adaptive antitumor immune responses. The activity of NK cells is regulated by functionally opposing, activating and inhibitory receptors whose balance ultimately determines whether target cells will be susceptible to NK cell mediated lysis. As melanoma is an immunogenic tumor, the effect of immunomodulating agents is consistently investigated. In this study in 79 metastatic melanoma (MM) patients and 52 controls NK activity, expression of activating NKG2D and CD161 receptors and KIR receptors, CD158a and CD158b, on freshly isolated PBL and NK cells were evaluated. Native NK cell activity of melanoma patients in clinical stage I-III and MM patients was determined against NK sensitive K562, NK resistant Daudi, human melanoma FemX, HeLa and HL 60 target tumor cell lines. In addition, predictive pretherapy immunomodulating effect after 18 h in vitro treatments of PBL of MM patients with rh IL-2, IFN-alpha (IFN), 13-cis retinoic acid (RA) and combination IFN-alpha and RA was evaluated with respect to NK cell lyses against K562 and FemX cell lines. In this study we show for the first time that low expression of CD161 and activating NKG2D receptors, without increased expression of KIR receptors CD158a and CD158b, as well as a decrease in the cytotoxic, CD16(bright) NK cell subset, is associated with a significant impairment in NK cell activity in MM patients. Furthermore, the predictive pretherapy finding that IL-2, IFN, IFN and RA, unlike RA alone, can enhance NK cell activity of MM patients against FemX melanoma tumor cell line can be of help in the design and development of therapeutic regimens, considering that it has recently been shown that low-dose combination of different immunomodulators represents the most promising approach in the therapy of MM.

We believe that determination of TNF-alpha in cystic fluid simultaneously with other parameters can be an additional parameter for clinical diagnosis of inflammed cysts.

In metastatic melanoma (MM) patients we evaluated natural killer (NK)-cell activity, distribution of several NK receptors and their correlation with NK function. Peripheral blood lymphocytes (PBL) of MM patients and controls were analysed for NK activity and expression of activating NKG2D, CD161 and KIR, CD158a and CD158b receptors on CD3-CD16+ NK cells. MM patients not only had significantly decreased NK activity and NK-cell interferon (IFN)-gamma production, a redistribution of NK-cell subsets with an increase in CD16(dim) and a reduction in CD16(bright) NK subsets. There was a decreased CD161 and NKG2D and an increased CD158a NK-cell expression in MM patients, with a positive correlation between NKG2D expression and NK cytotoxicity and an inverse correlation between CD158b expression and NK-cell cytotoxicity in patients. Furthermore, patients' CD3-CD16(bright) NK subset showed lower expression of CD161 and CD158a. Therefore, NKG2D, CD158a and CD158b expression in MM patients may represent several clinically useful 'biomarkers' of suppressed NK function.

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Recently, epidermal growth factor receptor (EGFR) was a key molecule in investigation of lung cancer, and it was a target for a new therapeutic strategy, based on molecular analyses. In this review, we have summarized some issues considering the role of EGFR in lung cancer, its coding gene, and its promoter gene polymorphisms (SNPs) -216G/T and -191C/A in non-small-cell lung cancer (NSCLC). The position of the SNPs indicates their significant role in EGFR regulation. The accumulation of knowledge regarding SNPs lately suggests their significant and important role in the onset of carcinogenesis, the prediction of the onset of metastases, the response to therapy with TKI inhibitors, and the onset of toxic effects of the applied therapy. Based on this, we suggest further studies of the relationship of clinical significance to SNPs in patients with lung tumors.