[Neoadjuvant therapy for resectable non-small cell lung cancer].

Treatment perspectives for non-small cell lung cancer (NSCLC) have been significantly expanded by the integration of immune checkpoint inhibitors into multimodal therapy concepts. Currently, combined, immune checkpoint-inhibitor-based therapy concepts are also advancing into early, resectable stages of NSCLC. Neoadjuvant and perioperative chemoimmunotherapy opened up a promising new preoperative treatment approach, but also raises some new questions and challenges.

Preventive Effect of Neuromuscular Training on Chemotherapy-Induced Neuropathy: A Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival.

Objective: To determine whether sensorimotor training (SMT) and whole-body vibration (WBV) training reduce symptoms and decrease the onset of CIPN.

Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients.

Introduction: Rearrangements of RET are rare oncogenic events in patients with non-small cell lung cancer (NSCLC). While the characterization of Asian patients suggests a predominance of nonsmokers of young age in this genetically defined lung cancer subgroup, little is known about the characteristics of non-Asian patients. We present the results of an analysis of a European cohort of patients with RET rearranged NSCLC.

Inhibition of protein geranylgeranylation specifically interferes with CD40-dependent B cell activation, resulting in a reduced capacity to induce T cell immunity.

Ab-independent effector functions of B cells, such as Ag presentation and cytokine production, have been shown to play an important role in a variety of immune-mediated conditions such as autoimmune diseases, transplant rejection, and graft-versus-host disease. Most current immunosuppressive treatments target T cells, are relatively unspecific, and result in profound immunosuppression that places patients at an increased risk of developing severe infections and cancer. Therapeutic strategies, which interfere with B cell activation, could therefore be a useful addition to the current immunosuppressive armamentarium.

The properties of human CD40-activated B cells as antigen-presenting cells are not affected by PGE2.

Tumor vaccination represents a promising immuno-therapeutic strategy in cancer. However, the inherent ability of many tumors to evade immune responses by suppression of immune cell function represents a major barrier. Prostaglandin E2 (PGE2) has been shown to be a critical tumor-derived immunosuppressive factor.

Results of a Phase II clinical trial with Id-protein-loaded dendritic cell vaccine in multiple myeloma: encouraging or discouraging?

Recently gained insight into the role of dendritic cells (DCs) as APCs has attracted the attention of many researchers who hope to use them as a tool in immunotherapy for the induction of tumor-specific immunity in cancer settings. Despite high expectations, in multiple myeloma patients the results of DC-based vaccines in terms of clinical response have been disappointing. The findings of Zahradova et al.

The immunosuppressive factors IL-10, TGF-β, and VEGF do not affect the antigen-presenting function of CD40-activated B cells.

Background: Progress in recent years strengthened the concept of cellular tumor vaccinations. However, a crucial barrier to successful cancer immunotherapy is tumor-mediated immunosuppression. Tumor-derived soluble factors such as IL-10, TGF-β, and VEGF suppress effector cells either directly or indirectly by disruption of dendritic cell (DC) differentiation, migration and antigen presentation.

Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis.

Background: More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis.

Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F]fluorodeoxyglucose and [(18)F]fluorothymidine positron emission tomography.

Purpose: Positron emission tomography (PET) with both 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) and 3'-[(18)F]fluoro-3'-deoxy-L-thymidine (FLT) was evaluated with respect to the accuracy of early prediction of nonprogression following erlotinib therapy, independent from epidermal growth factor receptor (EGFR) mutational status, in patients with previously untreated advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Thirty-four patients with untreated stage IV NSCLC were evaluated in this phase II trial. Changes in FDG and FLT uptake after 1 (early) and 6 (late) weeks of erlotinib treatment were compared with nonprogression measured by computed tomography after 6 weeks of treatment, progression-free survival (PFS), and overall survival (OS).

The shared tumor associated antigen cyclin-A2 is recognized by high-avidity T-cells.

Cyclin-A2, a key cell cycle regulator, has been shown to be overexpressed in various types of malignancies with little expression in normal tissue. Such tumor-associated genes potentially are useful targets for cancer immunotherapy. However, high-avidity cyclin-specific T cells are considered to be thymically deleted.

CD40-activated B cells can be generated in high number and purity in cancer patients: analysis of immunogenicity and homing potential.

Cellular adjuvants such as dendritic cells (DC) are in the focus of tumour immunotherapy. In DC-vaccine trials, induction of tumour antigen-specific immunity is observed frequently and well-documented clinical responses have been reported. However, the overall response rate is less than 3%, therefore alternative strategies are being investigated.

Activation of autologous leukemia-specific T cells in acute myeloid leukemia: monocyte-derived dendritic cells cocultured with leukemic blasts compared with leukemia-derived dendritic cells.

In acute myeloid leukemia (AML) blasts can be differentiated into dendritic cell (DC) like cells (AML-DC). These cells have a mature DC-like phenotype, are strong stimulators in mixed leukocyte reactions and can be used to generate leukemia-specific cytotoxic T cells. However, recent reports about naturally existing leukemic DC with immunoregulatory dysfunctions in peripheral blood of AML patients caused concerns about the use of AML-DC for therapeutic purposes.

Cytomorphologic signs of severe pernicious anemia obscured in a patient with heterozygous hemoglobin Stanleyville II.

Here, we report a rare coincidence of heterozygous hemoglobinopathy (Hb) Stanleyville II and severe pernicious anemia due to autoimmune gastritis. Hb Stanleyville II is characterized by a single base exchange (AAC-->AAA) resulting in a substitution Asn --> Lys at position 78 of hemoglobin alpha2-chain. Under normal conditions this hemoglobinopathy does not cause any symptoms even if present as homozygous variant.

Efficient activation of autologous tumor-specific T cells: a simple coculture technique of autologous dendritic cells compared to established cell fusion strategies in primary human colorectal carcinoma.

Different technologies have been employed to deliver the whole spectrum of tumor antigens (TAs) to dendritic cells (DCs) to be presented to T cells. These include whole tumor RNA-transfected DCs, preparations of DCs loaded with tumor-derived apoptotic bodies or tumor cell lysates, and DC tumor cell fusions. Early clinical trials have been conducted using such techniques.

German Hodgkin's Lymphoma Study Group trials: lessons from the past and current strategies.

Over the past decades, Hodgkin's lymphoma has become one of the most curable tumors in adults. This is mainly because of large clinical trials using risk-adapted, highly effective therapy modalities. For a long time, radiation therapy was the standard for treating patients with Hodgkin's lymphoma.

CD40-activated B cells express full lymph node homing triad and induce T-cell chemotaxis: potential as cellular adjuvants.

CD40-activated B cells (CD40-B cells) have previously been introduced as an alternative source of antigen-presenting cells for immunotherapy. CD40-B cells can prime naive and expand memory T cells, and they can be generated in large numbers from very small amounts of peripheral blood derived from healthy individuals or cancer patients alike. Administration of CD40-B cells as a cellular adjuvant would require these cells to migrate toward secondary lymphoid organs and attract T cells in situ, processes guided by specific chemokines and chemokine receptors.

A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells and CD138 activates NK cells and has potent antitumor activity against human multiple myeloma in vitro and in vivo.

The inability of the immune system to recognize and kill malignant plasma cells in patients with multiple myeloma (MM) has been attributed in part to the ineffective activation of natural killer (NK) cells. In order to activate and target NK cells to the malignant cells in MM we designed a novel recombinant bispecific protein (ULBP2-BB4). While ULBP2 binds the activating NK receptor NKG2D, the BB4 moiety binds to CD138, which is overexpressed on a variety of malignancies, including MM.

Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of patients with epithelial malignancies.

The detection of isolated tumor cells (ITC) in the bone marrow of patients with epithelial malignancies is an independant prognostic factor for several entities as breast cancer, colorectal cancer or non-small lung cancer. However, with conventional immunocytology using Ficoll density gradient and APAAP staining, only a small proportion of the bone marrow samples can be scanned for cytokeratin-positive (CK+) cells. To improve detection rates, we evaluated the enrichment of ITC by magnetic activated cell sorting (MACS) compared to regularly stained cytospins.

Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab.

The only established treatment for patients with thrombotic thrombocytopenic purpura (TTP) is plasma exchange against fresh frozen plasma. For cases refractory to plasma exchange, no generally treatment schedule exists. One option is immunosuppressive therapy with corticosteroids and vincristine.

Constitutive expression of c-FLIP in Hodgkin and Reed-Sternberg cells.

Crosslinking of the transmembrane receptor CD95/Fas leads to activation of a signaling cascade resulting in apoptosis. c-FLIP is a recently described protein that potently inhibits Fas-mediated apoptosis and has been shown to be a key factor in germinal center B cell survival. Because Hodgkin and Reed-Sternberg cells in classical Hodgkin's disease (cHD) are also resistant to Fas-mediated apoptosis we studied the role of c-FLIP in classical HD.

Cell fusion is not involved in the generation of giant cells in the Hodgkin-Reed Sternberg cell line L1236.

The mechanism of multinucleated cell formation in Hodgkin's disease has not yet been elucidated. We asked whether the giant multinucleated cells of the H-RS cell line L1236 develop via fusion of the predominant smaller cells. As a positive control for the fusion assay, human B cells from the B-cell lymphoma cell line BJA-B were split into two fractions, stained with the fluorochromes CMTMR and CMFDA, respectively, and fused using the polyethylene glycol 1500 cell hybridization protocol.

Immunomagnetic enrichment of CD138 positive cells from weakly infiltrated myeloma patients samples enables the determination of the tumor clone specific IgH rearrangement.

In multiple myeloma, the polymerase chain reaction (PCR) of the Ig heavy chain with allele-specific oligonucleotide (ASO) primers is a common and well-described method of identifying the tumor clone in peripheral blood (PB), bone marrow (BM) or leukapheresis products (LA). A factor which is crucial to the detection of clonal Ig rearrangements lies in the 'purity' of the tumor tissue used for the consensus PCR. We describe the application of a method to enrich CD138 positive myeloma cells derived from weakly infiltrated PB-, BM- and LA-samples.