Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation

Background Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. Methods We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. Results We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. Conclusions This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation

The relationship of potential biomarkers with psychological resilience and post-traumatic growth in female patients with breast cancer.

While investigating psychosocial factors on resilience and post-traumatic growth draws attention, research on biological correlates is limited. We investigated the relationship between post-traumatic growth, resilience, post-traumatic stress, and potential biomarkers in female patients with breast cancer (n = 71) from the general surgery or oncology clinics. They completed the Post-Traumatic Growth Inventory (PTGI), Connor Davidson Psychological Resilience Scale (CD-RISC), Brief Resilience Scale (BRS), PTSD Checklist for DSM-V, and Hospital Anxiety and Depression Scale. Blood samples were collected for NPY, ALLO, DHEA-S, testosterone, cortisol, and hsCRP levels. The relationship between biochemical parameters and the scales was investigated in the whole patient group and in the subgroup of patients who perceived breast cancer as traumatic. When all the patients were evaluated, hsCRP and depression scores were significantly and positively correlated; and hsCRP, BRS score, and PTGI change in self-perception subscale score were significantly and negatively correlated. There was a significant positive correlation between the ALLO level and the psychological resilience (CD-RISC) score in the patient group who perceived breast cancer as traumatic. It was observed that psychological resilience and PTG were positively correlated, and that multiple biomarkers were associated with psychological resilience in female breast cancer patients. Especially findings regarding ALLO levels and psychological resilience could be a new target for future research

Evaluation of Clinical Alvarado Scoring System and CT Criteria in the Diagnosis of Acute Appendicitis

Aim. The aim was to evaluate the clinical Alvarado scoring system and computed tomography (CT) criteria for the diagnosis of acute appendicitis. Material and Methods. 117 patients with acute abdominal pain who underwent abdominal CT were enrolled in this retrospective study. Patient demographics, clinical Alvarado scoring, CT images, and pathologic results of the patients were evaluated. Results. 39 of the 53 patients who were operated on had pathologically proven acute appendicitis. CT criteria of appendiceal diameter, presence of periappendiceal inflammation, fluid, appendicolith, and white blood cell (WBC) count were significantly correlated with the inflammation of the appendix. The best cut-off value for appendiceal diameter was 6.5 mm. The correlation between appendiceal diameter and WBC count was 80% (P=0.01<0.05). The correlation between appendiceal diameter and Alvarado score was 78.7% (P=0.01<0.05). Conclusion. Presence of CT criteria of appendiceal diameter above 6.5 mm, periappendiceal inflammation, fluid, and appendicolith should prompt the diagnosis of acute appendicitis. Since patients with acute appendicitis may not always show the typical signs and symptoms, CT is a helpful imaging modality for patients with relatively low Alvarado score and leukocytosis and when physical examination is confusing

Immune checkpoint status and exhaustion‐related phenotypes of CD8+ T cells from the tumor‐draining regional lymph nodes in breast cancer

Abstract Background Functional status of T cells determines the responsiveness of cancer patients to immunotherapeutic interventions. Even though T cell‐mediated immunity is inaugurated in the tumor‐adjacent lymph nodes, peripheral blood has been routinely sampled for testing the immunological assays. The purpose of this study is to determine the immune checkpoint molecule expression and the exhaustion‐related phenotype of cytotoxic T cells in the regional lymph nodes from breast cancer patients. Patients and methods Multicolor immunophenotyping was used to determine the expression of PD‐1, TIM‐3, LAG3, CTLA‐4, CCR7, CD45RO, CD127, CD25, CXCR5, and ICOS molecules on CD3+CD4−CD56−CD8+ cytotoxic T cells freshly obtained from the lymph nodes and the peripheral blood samples of the breast cancer patients. The results were assessed together with the clinical data. Results A population of cytotoxic T cells was noted with high PD‐1 and CXCR5 expression in the lymph nodes of the breast cancer patients. Co‐expression of PD‐1, CXCR5, TIM‐3, and ICOS indicated a follicular helper T cell (Tfh)‐like, exhaustion‐related immunophenotype in these cytotoxic T cells. Only a minor population with CTLA‐4 and LAG3 expression was noted. The PD‐1+CXCR5+ cytotoxic T cells largely displayed CD45RO+CCR7+ central memory markers. The amount of CXCR5‐expressing PD‐1− cytotoxic T cells was elevated in the lymph nodes of the patients. Conclusion The regional lymph nodes of breast cancer patients harbor Tfh‐like exhausted cytotoxic T lymphocytes with high PD‐1 and TIM‐3 checkpoint molecule expression. The immunological conditions in the regional lymph nodes should be implicated for immune checkpoint immunotherapy (ICI) of cancer

New Findings on Autoimmune Etiology of Idiopathic Granulomatous Mastitis: Serum IL-17, IL-22 and IL-23 Levels of Patients

Background Idiopathic Granulomatous Mastitis (IGM) is a benign chronic inflammatory breast disease that mimics breast cancer, and the etiopathogenesis has not yet been fully evaluated. Autoimmunity has received the most focus as a possible etiology. Our aim in this prospective clinical study was to investigate the possible association between the cytokines, interleukin IL-17, IL-22, IL-23 and IGM. Materials and Methods The current study was conducted in 26 women with histopathologically diagnosed IGM, and 15 control women of reproductive age having no breast disease history. Blood samples were collected, and serum concentrations of IL-17, IL-22, and IL-23 were determined. Results In the analysis of variables, the patients with IGM and the control group had statistically significant differences between serum IL-22 titers (p = 0.0378) and IL-23 titers (p = 0.0469. No statistically significant difference was found between IGM patients and the control group in serum IL-17 titers (p = 0.9724). Conclusion The results of the current study, especially pertaining to serum IL-22 and IL-23 levels, support the etiopathogenesis of IGM in favor of the autoinflammatory thesis. Nevertheless, this thesis should be supported by a large case number and prospective clinical studies

Comparison of lymph node metastasis rates in breast cancer molecular subtypes; A retrospective clinical study

Breast cancer is the most common cancer in women. Axillary lymph node metastasis in breast cancer is the most important determinant of long-term prognosis, but isn&apos;t an independent risk factor for overall survival. Invasive breast cancer is divided into molecular subtypes according to the presence of estrogen, progesterone and Her2 receptors: these subtypes can guide systemic therapy. Our aim in the study is to compare the axillary lymph node metastasis rates statistically in breast cancer subtypes. Patients treated for breast cancer were retrospectively evaluated in Group1(LuminalA-likeERand/orPR+,Her2 -), Group2 (LuminalB-likeER and/or PR+,Her2-), Group3 (Her2+,ER and/or PR+), Group4 (Her2+,ER and/or PR-) and Group5 (Her2-,ER and PR-) analyzed for tumor type, pathological stage, lymph node metastasis.208 patients were included in the study, and the mean age of the patients was 57.3±12.8. Although the age distribution of the groups was similar, no significant difference was found between the groups in terms of menopausal status. While the lymph node distribution was highly proliferative in Group 2. Demonstrating metastasis organotropisms in the effect of molecular subtypes of breast cancer is necessary to understand tumor mechanisms. ER and PR positive tumors usually metastasize to bones, while Her2+ or triple-negative breast cancers usually tend to metastasize to the visceral system, including the central nervous system. As with distant metastasis habits, lymph node metastasis rates of molecular subtypes of breast cancer can also vary. Being aware of these metastasis possibilities is also helpful in understanding the clinical behavior of the disease. It is important to know the molecular subtypes and susceptibility of lymphatic metastases as well as trying to avoid unnecessary complications of axillary dissection using the sentinel lymph node sampling technique. [Med-Science 2023; 12(1.000): 52-7

CT-guided tractography is a safe and complementary diagnostic tool in the management of penetrating abdominal trauma

Summary: Background/Objective: Despite extensive published research, the surgical approach to penetrating abdominal trauma patients is still under debate. Computed tomography-guided tractography (CTT) is an imaging modality in which water soluble iodinated contrast medium is administered into the site of the injury in the CT unit. The aim of this study was to determine the diagnostic accuracy of the CTT. Methods: A retrospective evaluation was made of patients admitted to the Emergency Department with penetrating abdominal trauma and who underwent CTT. Contrast enhanced abdominal CT and CTT reports, surgical findings and clinical results were examined. Results: Evaluation was made of a total of 101 patients comprising 89 males (88.1%) and 12 females (11.9%). CTT was determined to have 92.8% sensitivity, 93.6% specificity, 97% positive predictive value, and 85.5% negative predictive value. In 27 patients (26.7%) where the CTT indicated passage through the peritoneum, no parenchymal organ injury was present. Only one patient (2.9%) without peritoneal penetration on CTT had organ injury at exploration. No procedure-related morbidities developed. Conclusion: CTT is a safe imaging modality for the evaluation of hemodynamically stable patients. Compared to other imaging modalities, there is clearer demonstration of whether or not the peritoneum is intact. However penetration on CTT does not exactly correlate with organ injury. Keywords: Computed tomography guided tractography, Penetrating abdominal trauma, Therapeutic trauma laparotomy, Negative laparotom

Role of Intraoperative Nerve Monitoring in Postoperative Muscle and Nerve Function of Patients Undergoing Modified Radical Mastectomy

This study aimed to postoperatively evaluate the effects of intraoperative neural monitoring (IONM) on muscles and nerves in patients who underwent modified radical mastectomy (MRM). In the 11 patients included in the study, nerves were determined and protected by nerve monitoring during the axillary dissection (IONM group). In another 11 patients, nerve monitoring was not performed; however, protection of the same nerves was attempted through careful nerve dissection (cautious nerve dissection [CND] group). The control group consisted of 22 healthy subjects. Muscle and nerve functions were blindly evaluated by an experienced physical therapy and rehabilitation specialist using electromyography (EMG) and ultrasonography (US) methods. The EMG values of the pectoralis major muscle were similar in the IONM and control groups (1.97 mV/1.98 mV, p = 0.97) but significantly lower in the CND group (1.57 mV, p < 0.05). Significant differences were found in the US values of the pectoralis major and minor muscles between the IONM and CND groups. No significant difference was found between the IONM and control groups in terms of EMG values of the serratus anterior muscle. This is the first prospective randomized study to objectively evaluate preservation of the nerve through nerve monitoring and its functional results. Monitoring of nerves during MRM is of great importance in terms of demonstrating the positive effects on muscle and nerve functions

A positive feedback loop driven by fibronectin and IL-1 beta sustains the inflammatory microenvironment in breast cancer

Inflammatory alterations of the extracellular matrix shape the tumor microenvironment and promote all stages of carcinogenesis. This study aims to determine the impact of cellular fibronectin on inflammatory facets of tumor-associated macrophages (TAMs) in breast cancer. Cellular fibronectin (FN) harboring the alternatively spliced extra domain A (FN-EDA) was determined to be a matrix component produced by the triple-negative breast cancer (TNBC) cells. High levels of FN-EDA correlated with poor survival in breast cancer patients. The proinflammatory cytokine IL-1 beta enhanced the expression of cellular fibronectin including FN-EDA. TAMs were frequently observed in the tumor areas rich in FN-EDA. Conditioned media from TNBC cells induced the differentiation of CD206(+)CD163(+) macrophages and stimulated the STAT3 pathway, ex vivo. In the macrophages, the STAT3 pathway enhanced FN-EDA-induced IL-1 beta secretion and NF-kappa B signaling. In conclusion, our data indicate a self-reinforcing mechanism sustained by FN-EDA and IL-1 beta through NF-kappa B and STAT3 signaling in TAMs which fosters an inflammatory environment in TNBC