Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer.

Purpose: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICIs) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.

Experimental Design: We harnessed a variety of transcriptomic, spatial and functional assays to characterize the differential impact of neo-adjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to NACT-naïve HGSOC samples from 5 independent patient cohorts.

Trimodal prehabilitation in oncogynaecology.

Prehabilitation is a set of interventions aimed at increasing the patient's endurance and functional capacity before a planned stressful event (oncogynaecological surgery). Currently, prehabilitation is based on three main modalities which are: physiotherapy, nutritional support and psychological support, with others gradually being added. In studies published to date, a positive effect of combined preoperative intervention on the patient's postoperative recovery reduces the risk of perioperative and postoperative complications, shortening the hospital stay.

Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.

Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8 effector T (T) cells and TIM3PD1, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8 T cells.

Uterovesical fistula and its treatment in Sub-Saharan Africa.

Aim of the study to summarize the current information on diagnostic and treatment options for uterovesical fistula as a consequence of iatrogenic complication. Methods: Literature review of available information on surgical treatment options for uterovesical fistula resulting from previous caesarean section and comparison with our own experience in the developing world. Conclusion: Uterovesical fistula is an abnormal communication between the bladder and uterus.

Implementation of the ERAS protocol in gynecology and oncogynecology - evaluation of a pilot study.

Objective: To describe the implementation process and evaluate the success of compliance with the recommended ERAS protocol in the Czech healthcare system.

Methods: The study included 163 patients from March to September 2022, a total of 7 months. Patients were divided into three groups according to the type of surgery.

Experiences in the reconstruction of untreated severe obstetrical injuries including anal sphincter injuries.

Objective: Summarize information on reconstruction possibilities of extensive obstetrical injuries including anal sphincter injuries.

Methods: Review of available information on the possibilities of reconstruction of severe obstetrical injuries including anal sphincter and comparison with own results in the developing countries.

Conclusion: Extensive obstetrical injuries of the perineum are major problem that require adequate and early treatment.

Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines.

Dendritic cells (DCs) have received considerable attention as potential targets for the development of novel cancer immunotherapies. However, the clinical efficacy of DC-based vaccines remains suboptimal, largely reflecting local and systemic immunosuppression at baseline. An autologous DC-based vaccine (DCVAC) has recently been shown to improve progression-free survival and overall survival in randomized clinical trials enrolling patients with lung cancer (SLU01, NCT02470468) or ovarian carcinoma (SOV01, NCT02107937), but not metastatic castration-resistant prostate cancer (SP005, NCT02111577), despite a good safety profile across all cohorts.

An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors.

Purpose: The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937).

Uterine artery pseudoaneurysm in pregnant women with previous pelvic endometriosis.

Uterine artery pseudoaneurysm (UAP) is a rare complication during pregnancy that can cause serious consequences in both the pregnant woman and the fetus. Herein, we have described the cases of two pregnant women with UAP. Both patients had a history of laparoscopy for management of endometrioid ovarian cysts.

M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer.

Background: The immunological microenvironment of primary high-grade serous carcinomas (HGSCs) has a major impact on disease outcome. Conversely, little is known on the microenvironment of metastatic HGSCs and its potential influence on patient survival. Here, we explore the clinical relevance of the immunological configuration of HGSC metastases.

Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients.

Background: Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, is critical for the host immune system to mount spontaneous and therapy-driven anticancer immune responses. One of such signals, i.e.

Urinary tract morbidity after nerve-sparing radical hysterectomy in women with cervical cancer.

Introduction And Hypothesis: Nerve-sparing radical hysterectomy (NSRH) has been developed as a method of cervical cancer treatment to reduce surgical morbidity compared with radical abdominal hysterectomy. The aim of this study was to analyze the short- and long-term effects of NSRH on urinary tract function.

Methods: A study group of 117 patients underwent NSRH type C1 with pelvic lymphadenectomy for cervical cancer stages IB1-IB2 without adjuvant radiotherapy at our department.

TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer.

Purpose: In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial.

Experimental Design: We harnessed a retrospective cohort of 80 chemotherapy-naïve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8 T cells, CD20 B cells, DC-LAMP dendritic cells as well as by PD-1, CTLA4, LAG-3, and TIM-3 cells in relation with prognosis and function orientation of the tumor microenvironment.

Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients.

A high density of tumor-infiltrating CD8 T cells and CD20 B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP DCs is robustly associated with an immune contexture characterized by T1 polarization and cytotoxic activity.

Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines.

In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile.

Clinical relevance of regulatory T cells monitoring in the peripheral blood of ovarian cancer patients.

Background: Tregs play a suppressive role in the control of antitumour immunity. In this study we evaluated the relevance of prospective monitoring of peripheral blood regulatory T cells (Tregs) as a potential prognostic marker of future outcome of epithelial ovarian cancer in patients with or without a metronomic chemotherapy.

Methods: 46 patients diagnosed with the ovarian cancer were enrolled in the study and divided into groups according to the stage of the disease, outcome of the surgery and treatment received.

Dynamics of T-cell infiltration during the course of ovarian cancer: the gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T-cells.

The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. We studied the immune cells that infiltrated the tumor tissues of ovarian cancer patients at different stages of disease.

Human tumor cells killed by anthracyclines induce a tumor-specific immune response.

Immunogenic cell death is characterized by the early surface exposure of chaperones including calreticulin and HSPs, which affect dendritic cell (DC) maturation and the uptake and presentation of tumor antigens. It has also been shown that it is characterized by the late release of high mobility group box 1 (HMGB1), which acts through Toll-like receptor 4 (TLR4) and augments the presentation of antigens from dying tumor cells to DCs. Most of the data on immunogenic tumor cell death were obtained using mouse models.

Superoxide dismutase mimetic tempol inhibits hypoxic pulmonary vasoconstriction in rats independently of nitric oxide production.

Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of NO in HPV remains unclear.