Explore the vast range of titles available.

Abstract Background The safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV. Patients and Methods We analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients. Results Across all 5 studies, 140 (50.9%) patients had tumors with CD30 expression <10%, including 60 (21.8%) with undetectable CD30 by IHC. No significant differences were observed for any study in overall response rates between patients with CD30 expression ≥10% or <10%. Median duration of response was also similar in the CD30 ≥10% and <10% groups for all studies. Conclusions In this analysis of studies across a range of CD30-expressing lymphomas, CD30 expression alone, as measured by standard IHC, does not predict clinical benefit from BV, making the determination of a threshold level of expression uncertain. The safety and efficacy of brentuximab vedotin, an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with lymphoma. This article examines the relationship between CD30 expression level and clinical response to brentuximab vedotin.

Our understanding of the role of myeloid-derived suppressor cells (MDSCs) in cancer is becoming increasingly complex. In addition to their eponymous role in suppressing immune responses, they directly support tumor growth, differentiation, and metastasis in a number of ways that are only now beginning to be appreciated. It is because of this increasingly complex role that these cells may become an important factor in the treatment of human cancer. In this Review, we discuss the most pertinent and controversial issues of MDSC biology and their role in promoting cancer progression and highlight how these cells may be used in the clinic, both as prognostic factors and as therapeutic targets.

The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME), which inhibits antitumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC) play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an antitumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches, and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various preclinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.

Acute graft-versus-host disease (GVHD) is initially triggered by alloreactive T cells, which damage peripheral tissues and lymphoid organs. Subsequent transition to chronic GVHD involves the emergence of autoimmunity, although the underlying mechanisms driving this process are unclear. Here, we tested the hypothesis that acute GVHD blocks peripheral tolerance of autoreactive T cells by impairing lymph node (LN) display of peripheral tissue-restricted antigens (PTAs). At the initiation of GVHD, LN fibroblastic reticular cells (FRCs) rapidly reduced expression of genes regulated by DEAF1, an autoimmune regulator-like transcription factor required for intranodal expression of PTAs. Subsequently, GVHD led to the selective elimination of the FRC population, and blocked the repair pathways required for its regeneration. We used a transgenic mouse model to show that the loss of presentation of an intestinal PTA by FRCs during GVHD resulted in the activation of autoaggressive T cells and gut injury. Finally, we show that FRCs normally expressed a unique PTA gene signature that was highly enriched for genes expressed in the target organs affected by chronic GVHD. In conclusion, acute GVHD damages and prevents repair of the FRC network, thus disabling an essential platform for purging autoreactive T cells from the repertoire.

Immune checkpoint inhibitors (ICI) used for cancer immunotherapy were shown to boost the existing anti-tumor immune response by preventing the inhibition of T cells by tumor cells. Antibodies targeting two negative immune checkpoint pathways, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1), have been approved first for patients with melanoma, squamous non-small cell lung cancer (NSCLC), and renal cell carcinoma. Clinical trials are ongoing to verify the efficiency of these antibodies for other cancer types and to evaluate strategies to block other checkpoint molecules. However, a number of patients do not respond to this treatment possibly due to profound immunosuppression, which is mediated partly by myeloid-derived suppressor cells (MDSC). This heterogeneous population of immature myeloid cells can strongly inhibit anti-tumor activities of T and NK cells and stimulate regulatory T cells (Treg), leading to tumor progression. Moreover, MDSC can contribute to patient resistance to immune checkpoint inhibition. Accumulating evidence demonstrates that the frequency and immunosuppressive function of MDSC in cancer patients can be used as a predictive marker for therapy response. This review focuses on the role of MDSC in immune checkpoint inhibition and provides an analysis of combination strategies for MDSC targeting together with ICI to improve their therapeutic efficiency in cancer patients.

Health implications to the population due to the consumption of contaminated vegetables has been a great concern all over the world. In this study, the levels of heavy metals (Cr, Cd, Zn, Fe, Pb, As, Mn, Cu, Hg, Ni and Co) in soil and commonly consumed vegetables from Mojo area in central Ethiopia have been determined using Inductively Coupled Plasma Optical Emission Spectrophotometer (ICP-OES) and possible health risks due to the consumptions of the vegetables have also been estimated. The levels of As, Pb, Cd, Zn, Cu, Hg and Co were exceeded the reference level in agricultural soil. Likewise, As, Pb, Cd, Cr and Hg levels exceeded the recommended values in vegetable samples with concentrations ranging from 1.93-5.73, 3.63-7.56, 0.56-1.56, 1.49-4.63 and 3.43-4.23 mg/kg, respectively. It was observed that leafy vegetable (cabbage) has accumulated heavy metals to greater extent compared with tomato. The estimated daily intake (EDI) of toxic metals due to the consumption of the vegetables were below the maximum tolerable daily intake (MTDI). However, the total health quotient (THQ), calculated based on EDI of the heavy metals were found > 1 for As and Hg due to tomato consumption and for As, Hg and Co due to cabbage consumption, suggesting significant health risk. The health index (HI) due to the intake of toxic metals from the consumption of both vegetables were much > 1, with HI values of 7.205 and 15.078 due to tomato and cabbage consumption, respectively. This clearly suggests the possible adverse health effect to adult population from the consumption of tomato and cabbage from the study area. The total cancer risk (TCR) analysis have also revealed the potential adverse cancer risk induced by As, Cd, Hg, and Ni from the consumption of both tomato and cabbage as their TCR values were above the threshold level. Based on the results of this study, there would be a significant health risk (both non-carcinogenic and carcinogenic) to the consumer associated with the consumption of cabbage and tomato being cultivated in Mojo area. Consequently, we recommend a strict regulatory control on the safety of vegetables originated from the study area.

Key Points Synovial tissue is the target tissue for autoimmune arthritides such as rheumatoid arthritis. Synovial biopsy is a safe and well-tolerated procedure that is becoming more widely available. There is a significant body of work from the past 30 years analysing the cellular and molecular changes in synovial tissue from patients with rheumatoid arthritis to identify specific biomarkers. Technological advances in molecular and cellular analysis now provide new opportunities for defining new biomarkers and targets. Advances in synovial tissue research have improved our understanding of inflammatory arthritides, particularly rheumatoid arthritis, and have identified potential biomarkers that could be used for diagnosis, disease stratification, and predicting disease course and treatment response. The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis and stratification, as well as in predicting disease course and treatment response.