Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy.

New immunotherapeutic strategies are needed to induce effective antitumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppression, angiogenesis, and tumor aggressiveness.

Efficacy of Tumor Vaccines and Cellular Immunotherapies in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Purpose: Programmed cell death protein-1- checkpoint blockers have recently been approved as second-line treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, only a subgroup of patients responds and shows long-term survival to these therapies. Tumor vaccines and cellular immunotherapies could synergize with checkpoint blockade, but which of these treatments is most efficacious is unknown.

Pleural Effusion of Patients with Malignant Mesothelioma Induces Macrophage-Mediated T Cell Suppression.

Introduction: Clinical studies have demonstrated beneficial effects of immunotherapy in malignant pleural mesothelioma. The pleural cavity seems an attractive compartment to administer these types of therapies; however, local immunosuppressive mechanisms could hamper their efficacy. Macrophages are abundantly present within the mesothelioma microenvironment.

Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients.

Objectives: Clinical studies have proven the potential of immunotherapy in malignancies. To increase efficacy, a prerequisite is that treatment is tailored, so precision immune-oncology is the logical next step. In order to tailor treatment, characterization of the patient's tumor environment is key.

Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma.

Rationale: We demonstrated previously that autologous tumor lysate-pulsed dendritic cell-based immunotherapy in patients with malignant pleural mesothelioma is feasible, well-tolerated, and capable of inducing immunologic responses against tumor cells. In our murine model, we found that reduction of regulatory T cells with metronomic cyclophosphamide increased the efficacy of immunotherapy.

Objectives: To assess the decrease in number of peripheral blood regulatory T cells during combination therapy of low-dose cyclophosphamide and dendritic cell immunotherapy and determine the induction of immunologic responses with this treatment in patients with mesothelioma.

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer.

Myeloid-derived suppressor cells (MDSCs) play an important role in immune suppression and accumulate under pathologic conditions such as cancer and chronic inflammation. They comprise a heterogeneous population of immature myeloid cells that exert their immunosuppressive function via a variety of mechanisms. Immunoglobulin-like transcript 3 (ILT3) is a receptor containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) that can be expressed on antigen-presenting cells and is an important regulator of dendritic cell tolerance.

Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma.

Objectives: In patients with malignant pleural mesothelioma (MPM), local tumor outgrowth (LTO) after invasive procedures is a well-known complication. Currently, no biomarker is available to predict the occurrence of LTO. This study aims to investigate whether the tumor macrophage infiltration and phenotype of and/or the infiltration of CD8+ T-cells predicts LTO.

Immunotherapy prospects in the treatment of lung cancer and mesothelioma.

A very recent finding is the role of immune activation in cancer. The assumption that stimulating the patient's immune system to attack tumors is a valuable treatment option in malignant diseases has gained more acceptance. However the high immunosuppressive effects caused by the tumor limits this beneficial effect.

Ratio of intratumoral macrophage phenotypes is a prognostic factor in epithelioid malignant pleural mesothelioma.

Hypothesis: The tumor micro-environment and especially the different macrophage phenotypes appear to be of great influence on the behavior of multiple tumor types. M1 skewed macrophages possess anti-tumoral capacities, while the M2 polarized macrophages have pro-tumoral capacities. We analyzed if the macrophage count and the M2 to total macrophage ratio is a discriminative marker for outcome after surgery in malignant pleural mesothelioma (MPM) and studied the prognostic value of these immunological cells.

Immunomodulation in cancer.

We have to strengthen our 'chess-playing skills' when using immunotherapeutic approaches in cancer treatment: know the cancerous opponent, study its evolution and have an eye for its weaknesses. Besides tumor cells, other pieces on the board are stromal cells, endothelial cells and different immune cells. Some of these immune cells, like helper and cytotoxic T cells, natural killer (T) cells and mature dendritic cells are of help, others like regulatory T cells and myeloid-derived suppressor cells belong to the opponent, while macrophages and neutrophils can belong to both.

Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma.

Background: In 2001, it was postulated that tumour-derived exosomes could be a potent source of tumour-associated antigens (TAA). Since then, much knowledge is gained on their role in tumorigenesis but only very recently tumour-derived exosomes were used in dendritic cell (DC)-based immunotherapy. For this, DCs were cultured ex-vivo and loaded with exosomes derived from immunogenic tumours such as melanoma or glioma and re-administrated to induce anti-tumour responses in primary and metastatic tumour mouse models.

Immunological profiling as a means to invigorate personalized cancer therapy.

Immunotherapy has taken off but has not yet reached its cruising altitude and is certainly far from its final destination. Identifying the unique immunological profile of individual cancer patients will provide critical clues for the design of optimal strategies that rectify tumor-induced immune imbalances.

Tumor-specific cytotoxic T cells are crucial for efficacy of immunomodulatory antibodies in patients with lung cancer.

There is growing evidence that activation of the immune system may be an effective treatment for patients with either small cell lung cancer or non-small cell lung cancer (NSCLC). Immunomodulatory antibodies directed against cytotoxic T cell-associated antigen 4 (CTLA-4/CD152) and programmed cell death ligand 1 (PDL1/CD274) showed clinical efficacy in patients with lung cancer. The key immune cells responsible for antitumor activity are the CTLs.

Improving lung cancer survival; time to move on.

Background: During the past decades, numerous efforts have been made to decrease the death rate among lung cancer patients. Nonetheless, the improvement in long-term survival has been limited and lung cancer is still a devastating disease.

Discussion: With this article we would like to point out that survival of lung cancer could be strongly improved by controlling two pivotal prognostic factors: stage and treatment.

Patient-tailored modulation of the immune system may revolutionize future lung cancer treatment.

Cancer research has devoted most of its energy over the past decades on unraveling the control mechanisms within tumor cells that govern its behavior. From this we know that the onset of cancer is the result of cumulative genetic mutations and epigenetic alterations in tumor cells leading to an unregulated cell cycle, unlimited replicative potential and the possibility for tissue invasion and metastasis. Until recently it was often thought that tumors are more or less undetected or tolerated by the patient's immune system causing the neoplastic cells to divide and spread without resistance.

Dendritic cell-based immunotherapy in mesothelioma.

Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treatment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunotherapeutic strategies to improve the prognosis of patients with mesothelioma.

History of tuberculosis as an independent prognostic factor for lung cancer survival.

Introduction: It is well known that pulmonary tuberculosis is associated with an increased risk of lung cancer. We investigated whether a history of pulmonary tuberculosis is an independent risk factor for lung cancer survival in Caucasian patients.

Methods: The data of the prospective population-based cohort of The Rotterdam Study were used.

[Exosomes and cancer].

Exosomes are a subtype of vesicles released by cells of both healthy and neoplastic origin. Preclinical studies suggest a role for tumour-derived exosomes in tumour progression, mainly through the transfer of RNA and proteins from tumour cells to other cells. The transfer of RNA and proteins by tumour-derived exosomes seems to mediate stimulation of angiogenesis and suppression of immune cells; in contrast, exosomes from healthy cells of the immune system appear to have anti-tumour characteristics.

Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B.

Background & Aims: Natural killer (NK) cells play a major role in anti-viral immunity as first line defense and regulation of virus-specific T cell responses. This study aimed to investigate phenotype and function of NK cells in patients with chronic hepatitis B virus (HBV) infection and to study the effect of anti-viral therapy.

Methods: Peripheral blood NK cells from 40 chronic HBV patients were compared to NK cells of 25 healthy controls.

COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function.

Background: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumour-derived factors (e.g.

Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activity.

Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved.

Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma.

Rationale: We previously demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with a prolonged survival rate in mice. However, the clinical relevance is still in question. To examine this, we designed a clinical trial using chemotherapy followed by antigen-pulsed dendritic cell vaccination in mesothelioma patients.

Protein profiling of pleural effusions to identify malignant pleural mesothelioma using SELDI-TOF MS.

Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic techno_logies can be utilized to discover changes in expression of pleural proteins that might have diagnostic value. The objective of this study was to detect protein profiles that could be used to identify malignant pleural mesothelioma with surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS).

Exosomes.

Exosomes are small natural membrane vesicles released by a wide variety of cell types into the extracellular compartment by exocytosis. The biological functions of exosomes are only slowly unveiled, but it is clear that they serve to remove unnecessary cellular proteins (e.g.