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Cancer Immunology, Immunotherapy : CII Jan 2024The emergence of malignant ascites (MA) indicates poor prognoses in patients with ovarian, gastrointestinal, breast, and pancreatic cancer. Interleukin-10 (IL-10) is a... (Review)
Review
The emergence of malignant ascites (MA) indicates poor prognoses in patients with ovarian, gastrointestinal, breast, and pancreatic cancer. Interleukin-10 (IL-10) is a pleiotropic cytokine with immunoregulatory effects in tumor microenvironment. The level of IL-10 in MA varied across cancer types and patients, influencing cancer progression and outcomes. Originating from various immune and cancer cells, IL-10 contributes to complex signaling pathways in MA. Systemic IL-10 administration, although the evidence of its efficacy on MA is limited, still emerges as a promising therapeutic strategy because it can increase CD8+ T cells cytotoxicity and invigorate exhausted CD8+ tumor infiltration lymphocytes (TILs) directly. IL-10 signaling blockade also demonstrates great potential when combined with other immunotherapies in MA treatment. We reviewed the levels, origins, and functions of IL-10 in malignant ascites and overviewed the current IL-10 signaling targeting therapies, aiming to provide insights for MA treatment.
Topics: Humans; Ascites; CD8-Positive T-Lymphocytes; Cytokines; Interleukin-10; Peritoneal Neoplasms; Tumor Microenvironment
PubMed: 38279997
DOI: 10.1007/s00262-023-03616-y -
BMC Cancer Dec 2023The main aim of this study was to establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary...
BACKGROUND
The main aim of this study was to establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis.
METHODS
Clinicopathological and follow-up data of 174 patients with clear cell and endometrial ovarian cancer were retrospectively extracted. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer for comparative analysis of clinicopathological characteristics and prognosis.
RESULTS
Average age and post-menopausal rate in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P < 0.05). Body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA19.9, stage, differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1β and Napsin A were not significantly different between the groups (P > 0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05).
CONCLUSION
Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy.
Topics: Humans; Female; Prognosis; Endometriosis; Retrospective Studies; Neoplasm Recurrence, Local; Ovarian Neoplasms; Adenocarcinoma, Clear Cell
PubMed: 38066448
DOI: 10.1186/s12885-023-11641-4 -
Proceedings of the Japan Academy.... 2024This review seeks to highlight and celebrate Professor Tomizo Yoshida's famous work on "Establishment and characterization of a rat ascites sarcoma, later named "Yoshida... (Review)
Review
This review seeks to highlight and celebrate Professor Tomizo Yoshida's famous work on "Establishment and characterization of a rat ascites sarcoma, later named "Yoshida ascites sarcoma". Considering the tremendous contribution of this ascites tumor system to the subsequent promotion of research on cancer biology and cancer chemotherapy, his paper should be regarded as a monumental one in the cancer field. The research was carried out during 1943 and the results were submitted to this Journal in October 1944, when Japan was approaching a debilitating defeat in World War II in August 1945. In 1947, when "Research on Ascites sarcoma" was first comprehensively introduced to researchers in a special lecture at the Annual Meeting of the Japanese Society of Pathology, the whole audience was deeply impressed and was encouraged to resume scientific activity in Japan.
Topics: Animals; Sarcoma; Rats; Humans; History, 20th Century; Ascites; Japan
PubMed: 38866478
DOI: 10.2183/pjab.100.021 -
Advanced Science (Weinheim,... Feb 2024Cells constantly sense and respond to not only biochemical but also biomechanical changes in their microenvironment, demanding for dynamic metabolic adaptation. ECM...
Cells constantly sense and respond to not only biochemical but also biomechanical changes in their microenvironment, demanding for dynamic metabolic adaptation. ECM stiffening is a hallmark of cancer aggressiveness, while survival under substrate detachment also associates with poor prognosis. Mechanisms underlying this, non-linear mechano-response of tumor cells may reveal potential double-hit targets for cancers. Here, an integrin-GSK3β-FTO-mTOR axis is reported, that can integrate stiffness sensing to ensure both the growth advantage endowed by rigid substrate and cell death resistance under matrix detachment. It is demonstrated that substrate stiffening can activate mTORC1 and elevate mTOR level through integrins and GSK3β-FTO mediated mRNA m A modification, promoting anabolic metabolism. Inhibition of this axis upon ECM detachment enhances autophagy, which in turn conveys resilience of tumor cells to anoikis, as it is demonstrated in human breast ductal carcinoma in situ (DCIS) and mice malignant ascites. Collectively, these results highlight the biphasic mechano-regulation of cellular metabolism, with implications in tumor growth under stiffened conditions such as fibrosis, as well as in anoikis-resistance during cancer metastasis.
Topics: Humans; Animals; Mice; Mechanistic Target of Rapamycin Complex 1; Anoikis; Signal Transduction; Glycogen Synthase Kinase 3 beta; TOR Serine-Threonine Kinases; Neoplasms; Integrins; Tumor Microenvironment; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 38041494
DOI: 10.1002/advs.202307206 -
BMC Cancer Jul 2023CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14CXCR2...
BACKGROUND
CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14CXCR2 monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function.
METHODS
Flow cytometry was used to analyze the proportion of the CD14CXCR2 subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14CXCR2 monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression.
RESULTS
A decrease in the proportion of the CD14CXCR2 monocyte subset was observed in HCC patients compared with healthy controls. CXCR2 monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2 monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression.
CONCLUSIONS
Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.
Topics: Humans; Ascites; Carcinoma, Hepatocellular; Down-Regulation; Immunologic Factors; Interleukin-8; Lipopolysaccharide Receptors; Liver Neoplasms; Monoacylglycerol Lipases; Monocytes
PubMed: 37403022
DOI: 10.1186/s12885-023-11109-5 -
Anticancer Research Feb 2024Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently...
BACKGROUND/AIM
Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently developed especially for malignant ascites; however, the actual clinical efficacy of KM-CART has been rarely reported.
PATIENTS AND METHODS
We performed 226 KM-CART procedures in 104 patients with malignant ascites in three hospitals from August 2013 to September 2018. Medical records were retrospectively reviewed for ascites data, related complications, symptoms before and after each CART and prognosis after the first CART. The modified Glasgow Prognostic Score (mGPS) was reviewed before every procedure, as an indicator of nutritional status.
RESULTS
Pancreatic cancer was the most common indication for the KM-CART procedure, followed by gastric cancer, hepatocellular carcinoma, ovarian cancer, and cholangiocarcinoma (five major diseases). The 50% survival times of these five major diseases after the first procedure were 25, 39, 31, 49, and 33 days, respectively. The mean survival time for all patients was 73.5 days, and 75.6 days for those with the five major diseases. All patients experienced symptomatic relief, and complications were rare. Repeated KM-CART was performed in 47.1% of the patients, most often in those with ovarian cancer (66.7%). Regarding the mGPS at the first CART procedure, 89% of patients were in the group with the poorest nutritional status. Patients who underwent KM-CART three or more times had longer survival than those who were treated once or twice.
CONCLUSION
Repeated KM-CART provides a survival benefit for patients with malignant ascites, even in cases of poor nutritional status.
Topics: Female; Humans; Ascites; Retrospective Studies; Peritoneal Neoplasms; Ovarian Neoplasms; Liver Neoplasms; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 38307557
DOI: 10.21873/anticanres.16850 -
Cureus Aug 2023Malignant peritoneal mesothelioma (MPM) is a rare tumor of the serous membranes of the peritoneum and has been linked to exposure to asbestos and other risk factors. The...
Malignant peritoneal mesothelioma (MPM) is a rare tumor of the serous membranes of the peritoneum and has been linked to exposure to asbestos and other risk factors. The clinical manifestations are vague, with a wide clinical spectrum, predominantly related to the abdominal involvement of the disease. Localized mesothelioma is an uncommon manifestation of the disease. Common symptoms include abdominal pain or abdominal distention, nausea, anorexia, and weight loss. Rarely, patients present with paraneoplastic syndrome. Due to the nonspecific symptoms, many patients already have advanced disease at the time of diagnosis. The authors report a case of a 75-year-old female patient who presented with symptoms of asthenia, anorexia, progressive paleness, and weight loss lasting five months. She reports later new-onset symptoms of diffuse abdominal pain and diarrhea associated with nausea. Laboratory tests showed anemia, mild leukocytosis, thrombocytosis, elevated C-reactive protein (CRP), and elevated liver enzymes. An abdominal and pelvic computed tomography (CT) scan revealed marked tissue thickening of an irregular and striated configuration of the leaflets and peritoneal reflections in an omental cake pattern, and a chest CT scan showed multiple bilateral pulmonary nodules, suggesting diffuse malignant disease. A CT-guided biopsy of a peritoneal implant was performed, establishing the diagnosis of malignant peritoneal mesothelioma. Due to rapid clinical deterioration, the patient did not receive any systemic treatment, surgery, or radiotherapy and was transitioned to comfort care. As in the presented case, most cases of MPM have diffuse peritoneal involvement at the time of diagnosis, although extra-abdominal involvement is very rare. This disease presentation is associated with high morbidity and mortality compared to cases of localized disease. There is no specific imaging diagnostic modality or valuable tumor markers for MPM. Although a CT scan remains important in the diagnostic approach, the changes found are not specific. Radiographically, MPM may present as mesenteric or parietal peritoneal nodules, visceral peritoneal thickening, ascites, or omental masses. Although these features may raise suspicion of MPM, a biopsy is necessary to confirm the diagnosis. Therefore, due to the rarity of this disease and its nonspecific signs or symptoms, MPM is difficult to diagnose, and the prognosis remains poor.
PubMed: 37664365
DOI: 10.7759/cureus.42902 -
International Journal of Surgery... Nov 2023Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing...
BACKGROUND
Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing the procedure's diagnostic accuracy, we aimed to systematically review the literature on operative techniques, followed by peritoneal lavage fluid assessment in gastric cancer patients. Specifically, we sought to indicate the most common characteristics of the procedure and cytological evaluation.
METHODS
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol for this systematic review was registered on PROSPERO database (CRD: 42022306746). On September 2022, a search was carried out using Embase, Medline ALL, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection.
RESULTS
The search identified 1632 studies on staging laparoscopy and 2190 studies on peritoneal fluid assessment. Some 212 studies were included. Open Hasson was the method of choice in accessing the peritoneal cavity in 65% of the studies, followed by establishing a pneumoperitoneum at 10-12 mmHg in 52% of reports. Most frequently, the patient was positioned supine (70%), while a 30° scope and three ports were used to assess the peritoneal cavity clockwise (72%, 77%, and 85%, respectively). Right and left upper abdomen quadrants were the predominant area of laparoscopic exploration (both 65%), followed by the primary tumor region (54%), liver and pelvis (both 30%), and small bowel and spleen (19% and 17%, respectively). Regions of peritoneal lavage and aspiration were limited to the pelvis (50%), followed by right and left upper abdomen quadrants (37.5% and 50%, respectively). No studies compared different methods of operative techniques or analysis of ascites/fluid.
CONCLUSIONS
This study indicates a high heterogeneity in the technique of staging laparoscopy and peritoneal fluid assessment in gastric cancer patients. Further research and initiatives to reach a consensus on the standardization of the procedure are warranted.
Topics: Humans; Stomach Neoplasms; Ascitic Fluid; Neoplasm Staging; Laparoscopy; Peritoneal Lavage
PubMed: 37581636
DOI: 10.1097/JS9.0000000000000632 -
Frontiers in Immunology 2023Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a... (Observational Study)
Observational Study
INTRODUCTION
Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity.
METHODS
In this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs).
RESULTS
Activated T cells showing features of partial exhaustion with a CD137CD39PD-1TIM-3CD45RACD62LCD95 surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137CD39PD-1TIM-3CD45RACD62LCD95 signature.
CONCLUSION
These data demonstrate that EOC is enriched in CD137CD39PD-1TIM-3CD45RACD62LCD95 T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches.
Topics: Humans; Female; T-Lymphocytes; Hepatitis A Virus Cellular Receptor 2; Programmed Cell Death 1 Receptor; Carcinoma, Ovarian Epithelial; Leukocyte Common Antigens; Ovarian Neoplasms; Myeloid Cells; Tumor Microenvironment
PubMed: 37868997
DOI: 10.3389/fimmu.2023.1212444 -
Frontiers in Immunology 2024Malignant ascites indicates ovarian cancer progression and predicts poor clinical outcome. Various ascites components induce an immunosuppressive crosstalk between tumor...
INTRODUCTION
Malignant ascites indicates ovarian cancer progression and predicts poor clinical outcome. Various ascites components induce an immunosuppressive crosstalk between tumor and immune cells, which is poorly understood. In our previous study, imbalanced electrolytes, particularly high sodium content in malignant ascites, have been identified as a main immunosuppressive mechanism that impaired NK and T-cell activity.
METHODS
In the present study, we explored the role of high concentrations of ascites proteins and immunoglobulins on antitumoral NK effector functions. To this end, a coculture system consisting of healthy donor NK cells and ovarian cancer cells was used. The anti-EGFR antibody Cetuximab was added to induce antibody-dependent cellular cytotoxicity (ADCC). NK activity was assessed in the presence of different patient ascites samples and immunoglobulins that were isolated from ascites.
RESULTS
Overall high protein concentration in ascites impaired NK cell degranulation, conjugation to tumor cells, and intracellular calcium signaling. Immunoglobulins isolated from ascites samples competitively interfered with NK ADCC and inhibited the conjugation to target cells. Furthermore, downregulation of regulatory surface markers CD16 and DNAM-1 on NK cells was prevented by ascites-derived immunoglobulins during NK cell activation.
CONCLUSION
Our data show that high protein concentrations in biological fluids are able to suppress antitumoral activity of NK cells independent from the mechanism mediated by imbalanced electrolytes. The competitive interference between immunoglobulins of ascites and specific therapeutic antibodies could diminish the efficacy of antibody-based therapies and should be considered in antibody-based immunotherapies.
Topics: Humans; Killer Cells, Natural; Ascites; Female; Antibody-Dependent Cell Cytotoxicity; Ovarian Neoplasms; Cell Line, Tumor; Immunoglobulins; Receptors, IgG; Cell Degranulation; Antigens, Differentiation, T-Lymphocyte; Cetuximab
PubMed: 38646521
DOI: 10.3389/fimmu.2024.1360615