One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

Background: Acute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.

Main Body: This review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, including the immune checkpoint inhibitors (ICIs), monoclonal antibodies, and bispecific T-cell engagers (BiTE).

Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia.

Background: In recent decades, targeted therapy using small molecule inhibitors (SMI) have been shown very promising results in the treatment of a variety of solid and hematopoietic malignancies. However, their exact mechanisms, especiallay on the evasion strategies of tumor cells from the host immune system are not fully understood. The current study investigates the effects of two SMIs, ibrutinib and venetoclax, on the expression of inhibitory immune checkpoint molecules in patients with acute lymphoblastic leukemia (ALL).

SLAM receptors regulate immune checkpoints via SAP and EAT- 2 in rheumatoid arthritis: association with disease activity.

Objective: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and immune dysregulation. This study aimed to investigate the role of SLAM family receptors (SLAMF1 and SLAMF7), immune checkpoint molecules (PD- 1 and TIGIT), and SH2-containing adaptor proteins (SAP and EAT- 2) in rheumatoid arthritis (RA) and their association with disease activity.

Methods: A total of 50 RA patients (30 inactive, 20 active) and 20 healthy controls were enrolled.

JAK inhibitors as a promising therapy for immune-mediated photodermatoses.

Immune-mediated photodermatoses (IMPs) are skin diseases caused by altered immune responses triggered by sunlight, including polymorphous light eruption (PMLE), actinic prurigo (AP), solar urticaria (SU), chronic actinic dermatitis (CAD), and hydroa vacciniforme (HV). Managing IMPs is challenging because of the need for rigorous sun protection and the poor response to conventional therapies, particularly in moderate-to-severe patients. Researchers are exploring new targeted therapies for IMPs, including Janus kinase (JAK) inhibitors, a novel class of small molecules that block the JAK-STAT signaling pathway.

Effects of c-Kit Receptor, AKT, and NF-κB Inhibitors on Immune Evasion in Multiple Myeloma Cells.

Up-regulation of immune checkpoint ligands and secretion of soluble factors in the tumor microenvironment led to the survival of cancerous plasma cells in the bone marrow milieu. Therefore, we investigate the relationship between the inhibition of c-Kit receptor, AKT, and NF-κB signaling pathways and the regulation of immune escape mechanisms in multiple myeloma. The U266B1 cell line was treated with Masitinib as a c-Kit receptor inhibitor, Perifosine as AKT inhibitor, and Bortezomib as NF-κB inhibitor either in single or combined form.

Infiltration of innate and adoptive lymphoid cells in 4T1 and MC4-L2 breast cancer models.

Objectives: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that have vital roles in activating further immune responses. However, due to their tumor-induced diversity, we decided to examine ILCs, T cells, and the associated cytokines in mouse models of breast cancer.

Materials And Methods: 4T1 and MC4-L2 cells were used to induce triple-negative and hormone-receptor-positive breast cancer, respectively.

Clinical Significance of TNFSF14/LIGHT and CD160 in Gastric Cancer and Peptic Ulcer Dyspepsia.

Background: Previous studies have reported the role of the Herpes Virus Entry Mediator (HVEM) in various cancer including gastric cancer. However, the expression level and clinical significance of CD160 and Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14) pathways in gastric cancer and gastric dyspepsia patients have remained unexplored.

Methods: The study involved the collection of gastric tissue biopsies from 42 patients with non-ulcerative dyspepsia (NUD) as the control group, 43 gastric cancer (GC) patients, and 48 patients with peptic-ulcerative dyspepsia (PUD).

Cross-talk between leukemic and immune cells at the tumor microenvironment in chronic lymphocytic leukemia: An update review.

Chronic lymphocytic leukemia (CLL) is a mature-type B cell malignancy correlated with significant changes and defects in both the innate and adaptive arms of the immune system, together with a high dependency on the tumor microenvironment. Overall, the tumor microenvironment (TME) in CLL provides a supportive niche for leukemic cells to grow and survive, and interactions between CLL cells and the TME can contribute to disease progression and treatment resistance. Therefore, the increasing knowledge of the complicated interaction between immune cells and tumor cells, which is responsible for immune evasion and cancer progression, has provided an opportunity for the development of new therapeutic approaches.

Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via Combinational PI3K/AKT/mTOR Pathway Inhibitors.

Background: Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells.

Methods: HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination.

Three-dimensional bioengineered dermal derived matrix scaffold in combination with adipose-derived stem cells accelerate diabetic wound healing.

Due to the multifactorial nature of diabetic wounds, the most effective treatments require combinatorial approach. Herein we investigated whether engraftment of a bioengineered three-dimensional dermal derived matrix scaffold (DDMS) in combination with adipose-derived stem cells (ADSs), could accelerate diabetic wound healing. Diabetic animals were randomly planned into the control group, DDMS group, ADS group, and DDMS+ADS group.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

Background: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

Combination therapy of acute myeloid leukemia by dual PI3K/mTOR inhibitor BEZ235 and TLR-7/8 agonist R848 in murine model.

Background: Due to the high relapse rate and toxicity of the common therapies in patients with acute myeloid leukemia (AML), modifications in the treatment strategies are required. The present study was conducted to determine the effects of combinational therapy with a dual PI3K/mTOR inhibitor, BEZ235, and TLR7/8 agonist, R848, on murine AML model.

Methods: BEZ235 and R848 were administered to AML leukemic mice in either a single or combination treatment.

Exosomes derived from human placental mesenchymal stem cells in combination with hyperbaric oxygen synergically alleviates spinal cord ischemia-reperfusion injury.

Spinal cord ischemia-reperfusion injury (IR) is a terrible non-traumatic injury that occurs after abdominal aortic occlusion and causes serious damage to neurological function. Several treatment strategies have been suggested for IR, but they were not unable to effectively improve these conditions. Herein we investigated whether exosomes derived from human placental mesenchymal stem cells (hpMSCs-Exos) in combination with hyperbaric oxygen (HBO) could alleviate injury and promote recovery in IR rats.

Exosomes derived from human adipose mesenchymal stem cells loaded bioengineered three-dimensional amniotic membrane-scaffold-accelerated diabetic wound healing.

The occurrence of wounds and defects in the healing process is one of the main challenges in diabetic patients. Herein, we investigated whether adipose-derived stem cells (ADSCs)-derived exosomes loaded bioengineered micro-porous three-dimensional amniotic membrane-scaffold (AMS) could promote healing in diabetic rats. Sixty diabetic rats were randomly allocated into the control group, exosome group, AMS group, and AMS + Exo group.

Current Approaches of Immune Checkpoint Therapy in Chronic Lymphocytic Leukemia.

Increasing understanding of the complex interaction between leukemic and immune cells, which is responsible for tumor progression and immune evasion, has paved the way for the development of novel immunotherapy approaches in chronic lymphocytic leukemia (CLL). One of the well-known immune escape mechanisms of tumor cells is the up-regulation of immune checkpoint molecules. In recent years, targeting immune checkpoint receptors is the most clinically effective immunotherapeutic strategy for cancer treatment.

Association between Human Papillomavirus and Oral Cancer in Iranian Clinical Samples: A Meta-Analysis Review.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and is a serious problem worldwide. The role of HPV in oral cavity squamous cell carcinoma has been studied in several researches. This present review and meta-analysis aimed to investigate the relation between human papillomavirus (HPV) and oral cancer.

Expression Modulation of Immune Checkpoint Molecules by Ibrutinib and Everolimus Through STAT3 in MCF-7 Breast Cancer Cells.

Tumor-targeted therapy with small-molecule inhibitors (SMIs) has been demonstrated to be a highly effective therapeutic strategy for various cancers. However, their possible associations with immune evasion mechanisms remain unknown. This study examined the association of inhibitors of the protein kinase B (AKT), mammalian target of rapamycin (mTOR), and Bruton's tyrosine kinase (BTK) signaling pathways with the expression of immune checkpoint ligands programmed death-ligand 1 (PD-L1), CD155, and galectin-9 (Gal-9) in a breast cancer cell line.

The Effects of PI3K/Akt/mTOR Signaling Pathway Inhibitors on the Expression of Immune Checkpoint Ligands in Acute Myeloid Leukemia Cell Line.

Up-regulation of immune checkpoint ligands is considered as one of the most important immune escape mechanisms in acute myeloid leukemia (AML). Herein, we investigate a relationship between the inhibition of PI3K/Akt/mTOR signaling pathways and the regulation of immune checkpoint ligands in AML cells. The HL-60 cell line was treated with idelalisib as PI3K inhibitor, MK-2206 as Akt inhibitor, and everolimus as mTOR inhibitor either in a single or combined format.

Treatment by PI3K/mTOR Inhibitor BEZ235 Combined with TLR-7/8 Agonist Interfere with Immune Evasion Mechanisms of WEHI-3 Mouse Leukemia Cells.

Background: Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown.

Objectives: To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, and TLR7/8 agonist R848 on the expression and regulation of the immune inhibitory molecules in myeloid leukemia cells.

Cytokine profiling in Iranian patients with COVID-19; association with clinical severity.

Background: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients.

Objective: To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity.

Immune evasion mechanisms in acute myeloid leukemia: A focus on immune checkpoint pathways.

Immune surveillance mechanisms comprising of adaptive and innate immune systems are naturally designed to eliminate AML development. However, leukemic cells apply various immune evasion mechanisms to deviate host immune responses resulting tumor progression. One of the recently well-known immune escape mechanisms is over-expression of immune checkpoint receptors and their ligands.

Innate immune response in systemic autoimmune diseases: a potential target of therapy.

Innate immunity refers to defense mechanisms that are always present, ready to combat microbes and other offending agents. Innate immunity acts as a first-line defense and activates the conventional immune responses; however, it has been speculated that the importance of innate immunity in initiation and development of some disorders is more than just the "first line of defense". Autoimmune diseases, caused by immune system overactivation, are among the most challenging scientific and clinical problems, and there is still much to be learned about their pathogenesis.

Expression Analysis of Fyn and Bat3 Signal Transduction Molecules in Patients with Chronic Lymphocytic Leukemia.

Background: Chronic lymphocytic leukemia (CLL) is correlated with defects in T-cell function resulting imparity in antitumor immune responses. Tim-3 is a co-inhibitory immune checkpoint receptor expressed on exhausted T-cells during tumor progression. Fyn and Bat3 are two important adaptor molecules involved in inhibition and activation of Tim-3 downstream signaling, respectively.

Apoptosis and immunophenotyping of peripheral blood lymphocytes in Iranian COVID-19 patients: Clinical and laboratory characteristics.

A novel member of human coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been recently recognized in China and rapidly spread worldwide. Studies showed the decreasing of peripheral blood lymphocytes in a majority of patients. In this study, we have reported the clinical features, laboratory characteristics, the frequency of peripheral blood lymphocyte subpopulations, and their apoptosis pattern in Iranian coronavirus infectious disease (COVID-19) patients.