Immuno therapy

Immuno-oncology (IO) combination therapy is the first-line treatment for advanced renal cell carcinoma (RCC). However, biomarkers for predicting the response to IO combination therapy are lacking. Here, we investigated the association between the expression of soluble immune checkpoint molecules and the therapeutic efficacy of IO combination therapy in advanced RCC. The expression of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), soluble PD-L2 (sPD-L2), and lymphocyte activation gene-3 (sLAG-3) was assessed in plasma samples from 42 patients with advanced RCC who received first-line IO combination therapy...

Since the emergence of SARS-CoV-2 in late 2019, the global mortality attributable to COVID-19 has reached 6,972,152 deaths according to the World Health Organization (WHO). The association between coinfection with Clostridioides difficile (CDI) and SARS-CoV-2 has limited data in the literature. This retrospective study, conducted at Mureș County Clinical Hospital in Romania, involved 3002 ICU patients. Following stringent inclusion and exclusion criteria, 63 patients were enrolled, with a division into two subgroups-SARS-CoV-2 + CDI patients and CDI patients...

OBJECTIVE: Immuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored...

The potential prognostic influence of genetic aberrations on chronic lymphocytic leukaemia (CLL) can vary based on various factors, such as the immunoglobulin heavy variable (IGHV) status. We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next-generation sequencing in 536 CLL patients receiving first-line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status...

BACKGROUND: Immune checkpoint inhibitors (ICI) induce adverse events (irAEs) that do not respond to steroids, i.e. steroid-refractory (sr) irAEs, and irAEs in which steroids cannot be tapered, i.e. steroid-dependent (sd) irAEs, in about 10% of cases. An evidence-based analysis of the effectiveness of second-line immunosuppressive agents with regard to irAE and tumor control is lacking. METHODS: The international web-based Side Effect Registry Immuno-Oncology (SERIO; https://serio-registry...

BACKGROUND: An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms. METHODS: The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD...

INTRODUCTION: Hematopoietic progenitor kinase 1 (HPK1), a 97-kDa serine/threonine Ste20-related protein kinase, functions as an intracellular negative regulator, primarily in hematopoietic lineage cells, where it regulates T cells, B cells, dendritic cells and other immune cells. Loss of HPK1 kinase activity results in exacerbated cytokine secretion, enhanced T cell signaling, improved viral clearance, and thus increased restraint of tumor growth. These findings highlight HPK1 as a promising target for immuno-oncology treatments, culminating in the advancement of candidate compounds targeting HPK1 to clinical trials by several biotech enterprises...

BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7...

Collapsing focal segmental glomerulosclerosis (FSGS) a heterogeneous group of disorders, rather than a single disease entity. Kidney biopsy shows segmental or globally collapsed, sclerotic glomerular capillaries. There is also hypertrophy and hyperplasia of overlying glomerular epithelial cells. Immuno-fluorescence is negative or has non-specific deposits of immunoglobulins and C3. We present two cases of C3 dominant collapsing FSGS. Both the cases were non-responsive to therapy and had a poor outcome. This calls for research to study the role of the complement pathway in the pathogenesis of FSGS...

Human immunodeficiency virus (HIV) infection has historically been related to the development of specific cancers, some of which are so closely linked to the infection, such as Kaposi's Sarcoma (KS), that they have earned the name Acquired Immuno-Deficiency Syndrome (AIDS)-defining cancers (ADCs). While the development of antiretroviral therapy (ART) has decreased the incidence of AIDS-defining cancers, the resulting aging of people living with HIV (PLWH) highlighted an increased occurrence of other forms of cancer...

BACKGROUND: Tumors in the distal esophagus (EAC), gastro-esophageal junction including cardia (GEJAC), and stomach (GAC) develop in close proximity and show strong similarities on a molecular and cellular level. However, recent clinical data showed that the effectiveness of chemo-immunotherapy is limited to a subset of GEAC patients and that EACs and GEJACs generally benefit less from checkpoint inhibition compared to GACs. As the composition of the tumor immune microenvironment drives response to (immuno)therapy we here performed a detailed immune analysis of a large series of GEACs to facilitate the development of a more individualized immunomodulatory strategy...

OBJECTIVES: Mechanical valves still require life-long anticoagulation. Preclinical animal testing is a crucial step in the assessment of valves, however the chosen animal model should be carefully considered, and a well-controlled animal model of mechanical valve thrombosis has not been established yet. In this study, a histopathologic comparison was performed to evaluate the representativity of pigs and sheep as large animal models in bileaflet mechanical valve thrombosis research. METHODS: 10 pigs and 8 sheep were implanted with a bileaflet mechanical valve in pulmonary position...

Discovery research is the starting point for the development of more effective anti-cancer treatments. It requires an interdisciplinary research environment with first-class infrastructural support in which curiosity-driven research can lead to new concepts for treating cancer. Translating such research findings to clinical practice requires complementary skills and infrastructures, including high-quality clinical facilities, access to patient cohorts and participation of pharma. This complex ecosystem has yielded many new but also "me too" treatment regimens, especially in immuno-oncology resulting in an extremely high pricing of anti-cancer agents...

Pharmacotherapy options for chronic lymphocytic leukaemia (CLL) have expanded significantly in recent years. These options include chemotherapy, chemoimmunotherapy and signalling pathway inhibitors. A notable shift in the treatment landscape began with the widespread adoption of ibrutinib in 2016. This analysis of claims data focuses on understanding how the use of novel therapies has evolved in clinical practice over the past decade in Germany. Anonymized claims data (2010-2022) from German statutory health insurance was used, covering patient demographics, treatments, and prescriptions...

BACKGROUND: Hyperthermia can play a synergistic role with chemotherapy in combination therapy. Although the association between caspase activation, apoptosis, and pyroptosis have been published for both cisplatin (CDDP) and hyperthermia therapies independently, the interactions between these molecular pathways in combination therapy are unknown. The present study aimed to investigate the possible interactions between caspase 8 activation, apoptosis, and pyroptosis in combination therapy...

BACKGROUND: Therapies targeting PD1/PD-L1 pathway have revolutionized the treatment of lung cancer. However, anti-PD1/PD-L1 therapies have proven beneficial for only a select group of lung adenocarcinoma (LUAD) patients and generally do not work for immuno-cold tumors characterized by a lack of immune cell infiltration. Identifying novel biomarkers is vital to broad therapeutic options for LUAD patients with no response to anti-PD1/PD-L1 immunotherapies. METHODS: Our study has developed a novel strategy to identify a promising biomarker that addresses the limitations of anti-PD1/PD-L1 immunotherapy in treating immunological cold tumors...

BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that is capable of initiating an adaptive immune response. Induction of ICD may be a potential treatment strategy, as it has been demonstrated to activate the tumor-specific immune response. AIMS: The biomarkers of ICD and their relationships with the tumor microenvironment, clinical features, and immunotherapy response are not fully understood in a clinical context. Therefore, we conducted pan-cancer analyses of ICD gene signatures across 33 cancer types from The Cancer Genome Atlas database...

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells...

One kind of angioproliferative disorder is Kaposi's sarcoma (KS). Growth of spindle-shaped cells, edema, inflammation, and neoangiogenesis are its defining features. Because it lacks the typical indicators of malignancy, it is classified as an intermediate neoplasm. People who are immunocompromised, receiving organ transplants, or receiving antiretroviral therapy are linked to KS. Although lymph node involvement by KS is extremely uncommon, when it does occur, it usually manifests as either the epidemic form in (Human Immuno-deficiency) HIV-positive patients or the endemic form in Africans...

Immuno-oncology has gained momentum with the approval of antibodies with clinical activities in different indications. Unfortunately, for anti-PD (L)1 agents in monotherapy, only half of the treated population achieves a clinical response. For other agents, such as anti-CTLA4 antibodies, no biomarkers exist, and tolerability can limit administration. In this study, using publicly available genomic datasets, we evaluated the expression of the macrophage scavenger receptor-A (SR-A) (MSR1) and its association with a response to check-point inhibitors (CPI)...