Krzysztof Koper

The Analysis of Receptor-binding Cancer Antigen Expressed on SiSo Cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy

RCAS1 is involved in generating the suppressive profile of the tumor microenvironment that helps cancer cells evade immune surveillance. The status of the cells surrounding the cancer nest may affect both the progression of the cancer and the development of metastases. In cases of ovarian cancer, a large number of patients do not respond to the applied therapy. The patient’s response to the applied therapy is directly linked to the status of the tumor microenvironment and the intensity of its suppressive profile. We analyzed the immunoreactivity of RCAS1 on the cells present in the ovarian cancer microenvironment in patients with the disease; these cells included macrophages and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity levels within these cells, taking into consideration the clinical stage of the cancer and the therapeutic strategy applied, such as the number of chemotherapy regiments, primary cytoreductive surgery, or the presence of advanced ascites. In the patients who did not respond to the therapy we observed significantly higher immunoreactivity levels of RCAS1 within the cancer nest than in those patients who did respond; moreover, in the non-responsive patients we found RCAS1 within both macrophages and carcinoma-associated fibroblasts. RCAS1 staining may provide information about the intensity of the immuno-suppressive microenvironment profile found in cases of ovarian cancer and its intensity may directly relate to the clinical outcome of the disease.

Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer - a preliminary report.

Citation Wicherek L, Jozwicki W, Windorbska W, Roszkowski K, Lukaszewska E, Wisniewski M, Brozyna AA, Basta P, Skret‐Magierlo J, Koper K, Rokita W, Dutsch‐Wicherek M. Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer – a preliminary report. Am J Reprod Immunol 2011; 66: 444–450

The Immunohistochemical Analysis of Antigens such as RCAS1 and B7H4 in the Cervical Cancer Nest and within the Fibroblasts and Macrophages Infiltrating the Cancer Microenvironment

The presence of the aggressive phenotype of the tumor seems to be indicated by the local infiltration of cancer cells and by the development of metastases in the lymph nodes. This phenotype is related to the intensity of the suppressive profile of the tumor microenvironment. The aim of our study has been to gather information about the expression of both RCAS1 and B7H4 proteins in the macrophages and fibroblasts present within both the microenvironment of cervical cancer tumors and the cancer cells present on the front of the cancer nest.

The analysis of metallothionein immunoreactivity in stromal fibroblasts and macrophages in cases of uterine cervical carcinoma with respect to both the local and distant spread of the disease.

The tumor microenvironment is made up of tissue that is responsible for the growth and progression of the tumor as well as its ability to initiate metastases. The cancer cells on the front of the tumor together with the macrophages and fibroblasts help to constitute the aggressive phenotype of the tumor. The presence of this aggressive phenotype is indicated by the local infiltration of cancer cells and by the development of lymph node metastases. In cases of uterine cancer, the extent of the local and distant spread of the disease is crucial for determining the type of therapeutic strategy to be applied – surgery alone, surgery followed by radio‐chemotherapy, or radio‐chemotherapy alone. In the interest of trying to improve the patients quality of life, different studies supporting the therapeutic model of surgery alone have been conducted. While the cancer cells on the tumor front together with the macrophages and the fibroblasts help to constitute the aggressive phenotype of the tumor, metallothionein (MT) has been shown to have both pro‐proliferative and anti‐apoptotic activities and to participate in microenvironment remodeling. The aim of the current study was to determine the levels of MT immunoreactivity in the uterine cervical cancer cells as well as in the stromal fibroblasts and macrophages of the tumor microenvironment with respect to the depth of the local invasion and the extent of the distant metastases, so that its potential predictive value as a therapeutic strategy for cervical cancer can be ascertained.

The biological role of Treg cells in ectopic endometrium homeostasis.

Although retrograde menstruation is observed in up to 90% of women, endometriosis actually develops in only 15% of women. There is considerable evidence in the literature that ectopic endometrial cells are able to evade immune surveillance and that the immune response in the microenvironment of ectopic lesions is limited. Endometriosis develops when a deficiency in the local immune response has been generated, and progression of the disease is related to the intensity of this process. Over the last couple of decades it has been well known that T regulatory lymphocytes (Tregs) play a crucial role in controlling a variety of physiological and pathological immune responses. In this review we have focused on the physiological alteration of Treg cell infiltration into the endometrium during the reproductive processes of women. We discuss how a disturbance in Treg cell expansion is involved in generating such pathological processes as miscarriage and ectopic pregnancy development. We hypothesize about the role Treg cells might play in the survival of endometriosis foci in ectopic localization and in the evasion of such lesions from host immune surveillance.

Microbiological monitoring in patients with advanced ovarian cancer before and after cytoreductive surgery – a preliminary report

Abstract Multidrug-resistant organisms (MDROs) are becoming an increasing problem in hospitals. It is believed that screening patients for the incidence of MDROs prior to hospital admission not only allows for the proper management of infection following medical procedures, but can also potentially reduce the transmission of these bacteria to other patients. The aim of this study was to assess the carriers of selected MDROs in the gastrointestinal tract among patients with advanced ovarian cancer admitted to the hospital for cytoreductive surgery and to estimate the possible relationship between rectal colonization with these organisms and nosocomial infections. From December 2013 to May 2014, we evaluated the colonization with VRE (vancomycin-resistant Enterococcus), E. coli KPC+ (class A carbapenemase producing Escherichia coli), E. coli MBL+ (class B carbapenemase, metallo-ß lactamase producing Escherichia coli), and E. coli ESBL+ (extended-spectrum ß-lactamase producing Escherichia coli) in 42 patients. The patients were divided into two subgroups corresponding to the extent of their surgery: the first subgroup consisted of patients with large bowel resection (n=18) and the second subgroup of patients without resection (n=24). A rectal swab was taken within 24 hours of admission. Perioperative infectious complications were analyzed for the first 90 days following surgery with regard to the type of infection and the occurrence of examined MDROs. In our study, 2.4 % of all patients (23.8/1,000 hospitalizations) were colonized with ESBL - producing Escherichia coli: 0.0 % in the first subgroup and 4.2% in the second subgroup, respectively. We did not identify any patients who were colonized with VRE, E. coli MBL+, or E. coli KPC+. Surgical site infections were seen in 8 (19.1%) out of 42 patients. We were, therefore, unable to confirm a relationship between MDROs colonizing the large bowel and the etiological agents of perioperative infections. However, despite the lack of identification of MDROs as etiological agents of postoperative infection, the risk of serious infectious complications, combined with the changing epidemiological situation, means that microbiological monitoring should be performed in patients with ovarian cancer before and after cytoreductive surgery.

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