Autoreactive napsin A-specific T cells are enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade.

Cancer treatment with immune checkpoint blockade (ICB) often induces immune-related adverse events (irAEs). We hypothesized that proteins coexpressed in tumors and normal cells could be antigenic targets in irAEs and herein described DITAS (discovery of tumor-associated self-antigens) for their identification. DITAS computed transcriptional similarity between lung tumors and healthy lung tissue based on single-sample gene set enrichment analysis.

Analysis of Coil Configurations for a Contactless Thermal Tumor Ablation With Implanted Devices.

In the wide field of tumor treatment, thermal ablation procedures are very promising. Alternating magnetic fields are used to transfer the energy from outside the patient to the tumor area located anywhere in the body. This energy is converted to heat by implanted devices located in the tumor area.

Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival.

Immune checkpoint inhibitors (ICIs) have improved the survival of patients with non-small cell lung cancer (NSCLC) by reinvigorating tumor-specific T cell responses. However, the specificity of such T cells and the human leukocyte antigen (HLA)-associated epitopes recognized, remain elusive. In this study, we identified NSCLC T cell epitopes of recently described NSCLC-associated antigens, termed keratinocyte differentiation antigens.

Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups.

We describe the results of two vaccinations of a self-experimenting healthy volunteer with SARS-CoV-2-derived peptides performed in March and April 2020, respectively. The first set of peptides contained eight peptides predicted to bind to the individual's HLA molecules. The second set consisted of ten peptides predicted to bind promiscuously to several HLA-DR allotypes.

Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program.

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib.

Patients And Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed.

Results: In total, 52 patients were included [median age 57 years (range 32-81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively.

Towards new horizons: characterization, classification and implications of the tumour antigenic repertoire.

Immune-checkpoint inhibition provides an unmatched level of durable clinical efficacy in various malignancies. Such therapies promote the activation of antigen-specific T cells, although the precise targets of these T cells remain unknown. Exploiting these targets holds great potential to amplify responses to treatment, such as by combining immune-checkpoint inhibition with therapeutic vaccination or other antigen-directed treatments.

A Non-interventional Clinical Trial Assessing Immune Responses After Radiofrequency Ablation of Liver Metastases From Colorectal Cancer.

Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells.

A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer.

Background: We previously showed that the bacterial lipopeptide PamCys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8 T cells in mice, when covalently coupled to a synthetic peptide.

Case Presentation: We now designed a new water-soluble synthetic PamCys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8 T and NK cells by 6-sulfo LacNAc monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays.

Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma.

Background: Although mutated HLA ligands are considered ideal cancer-specific immunotherapy targets, evidence for their presentation is lacking in hepatocellular carcinomas (HCCs). Employing a unique multi-omics approach comprising a neoepitope identification pipeline, we assessed exome-derived mutations naturally presented as HLA class I ligands in HCCs.

Methods: In-depth multi-omics analyses included whole exome and transcriptome sequencing to define individual patient-specific search spaces of neoepitope candidates.

Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer.

Background: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data sources and study eligibility criteria: A systematic literature search was performed in PubMed, with keywords "HIPEC" and "colorectal cancer", according to established guidelines.

First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications.

Background: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported.

Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation.

Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue.

Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells.

Platelets promote metastasis, among others by coating cancer cells traveling through the blood, which results in protection from NK cell immune-surveillance. The underlying mechanisms, however, remain to be fully elucidated. Here we report that platelet-coating reduces surface expression of NKG2D ligands, in particular MICA and MICB, on tumor cells, which was mirrored by enhanced release of their soluble ectodomains.

The immunopeptidomic landscape of ovarian carcinomas.

Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs).

Haploidentical hematopoietic cell transplantation using in vitro T cell depleted grafts as salvage therapy in patients with disease relapse after prior allogeneic transplantation.

Disease relapse after one or more allogeneic hematopoietic cell transplantations (HCT) represents a therapeutic challenge with all options bearing a significant morbidity and mortality. Haploidentical HCT may induce more pronounced anti-leukemic effects and was evaluated at our center in 25 consecutive patients with disease relapse after preceding HCT receiving haploidentical grafts after in vitro T cell depletion. Overall survival at 1 and 2 years was 32 and 14%, respectively.

Uric acid as a novel biomarker for bone-marrow function and incipient hematopoietic reconstitution after aplasia in patients with hematologic malignancies.

Purpose: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal.

Methods: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total).

Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies with application of cytostatic drugs such as oxaliplatin (OX) after cytoreductive surgery. Despite its increased use, evidence for optimal drug dosage, and notably duration of HIPEC, is scarce.

Methods: In this study, OX distribution was comprehensively assessed in nine patients during HIPEC (300 mg OX/m body surface area in Physioneal solution for 30 min).

Graft versus self (GvS) against T-cell autoantigens is a mechanism of graft-host interaction.

Graft-versus-host disease (GVHD) represents the major nonrelapse complication of allogeneic hematopoietic cell transplantation. Although rare, the CNS and the eye can be affected. In this study, manifestation in the retina as part of the CNS and T-cell epitopes recognized by the allogeneic T cells were evaluated.

[Hematologic chest pain].

History And Admission Findings: We report the case of a 59-year-old male who was admitted to hospital with acute chest pain. Coronary heart disease was known from the medical history. The patient reported recurrent ostealgia and susceptibility for infection during the last months before admission.

Soluble heat shock protein 70 members in patients undergoing allogeneic hematopoietic cell transplantation.

Background: Heat shock proteins (HSP) are highly conserved immunogenic proteins serving as potent danger signals. They are upregulated under stress conditions like fever and hypoxia. Extracellular HSP are involved in antigen presentation, cytokine release and maturation of antigen presenting cells.

Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab.

The epidermal growth factor receptor HER2/neu is expressed on various cancers and represents a negative prognostic marker, but is also a target for the therapeutic monoclonal antibody Trastuzumab. In about 30% of cases, HER2/neu is expressed on acute lymphoblastic leukemia (ALL) cells and was proposed to be associated with a deleterious prognosis. Here we evaluated clinical data from 65 ALL patients (HER2/neu+, n = 17; HER2/neu-, n = 48) with a median follow-up of 19.

Choroidal metastases from thymic carcinoma during pregnancy: Case Report.

Background: Rare sites of metastases, atypical symptoms and paraneoplastic syndromes are often neglected or misinterpreted, especially when they represent early symptoms of an underlying malignant disease. Hence, an interdisciplinary approach to these patients is essential to avoid tumor progression and metastatic spread in order to provide curative treatment options to the patients. We here report the case of a young woman presenting with visual loss which led to diagnosis of a thymic carcinoma.

Poor graft function can be durably and safely improved by CD34+-selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation.

Purpose: Insufficient production of leukocytes, thrombocytes and erythrocytes after allogeneic peripheral blood stem cell transplantation (PBSCT) represents a life-threatening complication.

Methods: In 20 adult patients with poor graft function (PGF defined as transfusion-dependent platelet counts <20,000/µl, or leukocytes <1500/µl, or transfusion-dependent anemia) and variable causes of PGF after allogeneic PBSCT, immunomagnetically selected CD34(+) stem cell boosts (SCB) from matched unrelated (n = 8), mismatched unrelated (n = 11) or haploidentical (n = 1) donors were applied without prior conditioning.

Results: Patients received a median of 4.

The repertoire of human tumor-associated epitopes--identification and selection of antigens and their application in clinical trials.

In cancer patients, active immunotherapy has gained significant importance in recent years by implementation of novel substances into standard clinical care. These new drugs represent strategies which either use defined cancer associated antigens as vaccines or induce tumor-directed immune responses through generation of a general inflammatory state which has extensive autoinflammatory side effects by induction of autoreactive immune cells. Hence, the definition of suitable target antigens for immunotherapy remains a major challenge.