CONTENTS
Reviews
- Is Tumor Expression of the Major Histocompatibility Complex Antigen Required for T Cell Immune Surveillance?
Yang Liu and Pan Zheng (Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA)Abstract. Tumor expression of major histocompatibility complex antigen (MHC) class I and class II is not essential for the induction of memory T cells. However, induction of MHC class I-restricted effector cytotoxic T cells (CTL) appears dependent on MHC class I expression on tumors. Moreover, the effector function of tumor-specific CTL requires direct recognition of the tumor. In contrast, both the inductive and the effector phases of MHC class II-restricted T cells are independent of MHC class II expression on tumors.
Keywords: tumor immunity; major histocompatibility complex; immune surveillance; antigen-presentation; cross-priming
- Chronic Hepatitis C Virus Infection and the Pathogenesis of Hepatocellular Carcinoma
Mark Feitelson (Department of Pathology, Anatomy and Cell Biology, Department of Microbiology and Immunology, Kimmel Cancer Center Thomas Jefferson University, Philadelphia, PA 19107, USA)Abstract. There is a strong epidemiologic relationship between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), although the cellular and molecular mechanisms of tumor formation remain to be firmly established. Clearly, HCV is associated with the development of chronic hepatitis and cirrhosis, so that it may contribute to hepatocarcinogenesis as a consequence of its central role in the appearance and progression of necroinflammatory liver disease. There is also increasing evidence for a direct contribution of several HCV gene products to the development of the transformed phenotype, although none of the putative mechanisms involved in tumor formation have been strongly supported by in vivo evidence. Even if HCV is not shown to be a complete carcinogen, it may act as a cocarcinogen with underlying (serologically negative) hepatitis B virus (HBV) infection, in the context of alcoholic cirrhosis, and in patients with long term exposure to chemical hepatocarcinogens such as aflatoxin B1.
Keywords: hepatitis C virus; hepatocellular carcinoma; tumor pathogenesis
- Immune Reaction to Breast Cancer: for Better or for Worse?
Helga M. Ögmundsdótti (Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik, Iceland)Abstract. The infiltration of breast carcinomas with lymphoid cells has often been interpreted as an indication of an active immune response against the tumor and thus a favorable prognostic sign. Several studies have, however, cast doubt on this assumption. In situ breast carcinomas are more common than invasive cancers and it may be speculated that immune surveillance plays a role in preventing some localized cancers from becoming invasive. A secondary type of immune surveillance might be implicated in the long persistence of dormant breast carcinoma cells in the bone marrow. Breast cancer cells can carry tumor-associated antigens, particularly MUC1. These may elicit specific antibody responses but there is less evidence for a CTL response. There are indications that professional antigen presenting cells may be present and active at the edge breast tumours. Breast cancer cells may also interact directly with macrophages and NK cells. In terms of immune effector mechanisms in breast cancer, the communication with potential effector cells is likely to be often faulty because of altered expression of HLA class I molecules. Pleiotrophic cytokines are frequently present and could have a variety of effects ranging from growth inhibition to stimulated proliferation, loss of cell adhesion and activation of matrix degrading enzymes. Fas ligand is unlikely to play a role in the immune evasion of breast cancer. There is thus evidence for a variety of immune reactions to breast cancer. It is possible that they mediate some form surveillance, but growing, invasive tumors have escape routes and may even use cytokines to their advantage.
Keywords: breast cancer; immune surveillance; tumor antigens; cytokines; Fas-FasL; immune evasion
Original papers
- Effect of Granulocyte-Macrophage Colony Stimulating Growth Factor on Interferon and Tumor Necrosis Factor Production in Whole Blood Cell Cultures of Patients with Acute Myelogenous Leukemia
Teresa Kamińska, Iwona Hus, Anna Dmoszyńska and Martyna Kandefer-SzerszeńAbstract. The effect of recombinant human granulocyte-macrophage colony-stimulating growth factor (rHuGM-CSF) treatement on in vitro interferon (IFN) and tumor necrosis factor (TNF) production in peripheral blood cells of 46 patients with acute myelogenous leukemia (AML) was examined. GM-CSF significant enhanced virus-induced IFN-a production in blood cells (containing 70% of blasts) of 28 patients with M4-M5 AML according to the French-American-British (FAB) classification and also phytohemagglutinin (PHA)-induced IFN-g production in blood cells (containing 68% of blasts) of 18 patients with AML M0-M3 type. In control blood cells (25 healthy persons) GM-CSF enhanced PHA-induced IFN-g but did not influence IFN-a production. In the presence of GM-CSF, TNF-a titers induced with lipopolysaccharide were also higher in control blood cells but not in cells of patients with M0-M3 or M4-M5 type of AML. The significance of GM-CSF-enhanced IFN-a and IFN-g production in antimicrobial and antileukemic immune reactions which can develop during GM-CSF therapy is discussed.
Keywords: acute myelogenous leukemia; GM-CSF; interferon; tumor necrosis factor
- Pre-Operative Levels of Serum Immunoglobulins, Circulating Immune Complexes and Complement Proteins in Patients with Different Types of Neoplasms
Hanna Gendek-Kubiak (1), Janina Grzegorczyk (2), Ewa G. Gendek (3), Marek L. Kowalski (2) and Jan Berner (4) – (1) Division of Cytophysiology, Department of Histology and Embryology, Medical University of Łódź, Narutowicza 60, 90-136 Łódź, Poland, (2) Department of Clinical Immunology and Allergy, Medical University of Łódź, Mazowiecka 11, 92-215 Łódź, Poland, (3) Institute of Technical Biochemistry, Technical University of Łódź, Stefanowskiego 4/10, 90-924 Łódź, Poland, (4) Department of Surgical Oncology, Medical University of Łódź, Paderewskiego 4, 93-509 Łódź, PolandAbstract. In the sera of 30 neoplasm patients without metastases, the average IgG level was higher than in the control group (CG) (18.16 + 5.10 versus 12.62 + 2.14 g/l or 12.22 + 2.14 after excluding an out-lier). Average concentrations of CIC, IgM, C1i, C3c and C4 did not statistically differ between the groups. Dividing the patients’ group into breast or ovary cancer (BC), melanoma (M), digestive tract cancer (DT) and other neoplasms (ON) subgroups revealed that the IgG increase did not apply to the BC group. Relatively decreased CIC concentrations in the BC and DT group and an increased C1i in the DT group were found. Several diversities detected in the humoral immunity indices’ distributions and correlations suggest activation of different mechanisms depending on the neoplasm types.
Keywords: neoplasm(s); immunoglobulin(s); complement; immune complexes
- Serum TNF-a Levels in the Neoplasm of Patients Qualified for Surgical Treatment
Hanna Gendek-Kubiak (1), Janina Grzegorczyk (2), Ewa G. Gendek (3), Marek L. Kowalski (2) and Jan Berner (4) – (1) Division of Cytophysiology, Department of Histology and Embryology, Medical University of Łódź, Narutowicza 60, 90-136 Łódź, Poland, (2) Department of Clinical Immunology and Allergy, Medical University of Łódź, Mazowiecka 11, 92-215 Łódź, Poland, (3) Institute of Technical Biochemistry, Technical University of Łódź, Stefanowskiego 4/10, 90-924 Łódź, Poland, (4) Department of Surgical Oncology, Medical University of Łódź, Paderewskiego 4, 93-509 Łódź, PolandAbstract. The aim of the study was to analyze serum tumor necrosis factor alpha (TNF-a) levels in different neoplasm types qualified for surgical treatment and to evaluate their possible correlations with circulating immune complexes (CIC), IgG, IgM, and thecomplement (C) compounds: C1 inhibitor (C1i), C3c and C4 levels. Studies were performed in sera from 30 neoplasm patients before surgical treatment and in 10 persons from a control group (CG) with no malignancy. Serum TNF-a levels were measured with the Cytogen ELISA kit. Average TNF-a levels measured in neoplastic patient groups qualified for surgical treatment were not significantly different from the average TNF-a level in the CG group.
Keywords: neoplasm(s); TNF-a; serum; surgery
- Characterization of NO and Cytokine Release by Transplantable Melanoma Cell Lines in Relationship to their Differentiation
Krystyna Kozłowska, Małgorzata Zarzeczna and Mirosława Cichorek (Department of Embryology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland)
Abstract. Changes in the secretory activity of two transplantable melanoma lines (differing in many biological features) as regards nitric oxide (NO) and interleukin 6 (IL-6), tumor necrosis factor a (TNF-a), oncostatin M (OSM) secretion were the subject of the present study. Obtained results show that a spontaneous alteration of the hamster’s native melanoma line in to an amelanotic one is accompanied by a global change of the secretory activity but there was not distinct correlation between the endogenous cytokine secretion and NO secretion by cells of both melanoma lines.
Keywords: NO; interleukin 6; tumor necrosis factor a; Oncostatin M; transplantable melanomas