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1.
Int J Mol Sci ; 23(7)2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1785725

ABSTRACT

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.


Subject(s)
Bioprinting , Neoplasms , Bioprinting/methods , Humans , Hydrogels , Precision Medicine , Printing, Three-Dimensional , Tissue Engineering/methods , Tissue Scaffolds , Tumor Microenvironment
2.
Int J Mol Sci ; 23(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1765735

ABSTRACT

B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.


Subject(s)
Lymphoma, B-Cell , Lymphoma , Lymphoproliferative Disorders , Humans , Immune System/pathology , Immunotherapy, Adoptive , Lymphoma/drug therapy , Lymphoma, B-Cell/therapy , Lymphoproliferative Disorders/pathology , Tumor Microenvironment
3.
Cells ; 11(6)2022 03 17.
Article in English | MEDLINE | ID: covidwho-1760409

ABSTRACT

Cancer therapy is an emergent application for mRNA therapeutics. While in tumor immunotherapy, mRNA encoding for tumor-associated antigens is delivered to antigen-presenting cells in spleen and lymph nodes, other therapeutic options benefit from immediate delivery of mRNA nanomedicines directly to the tumor. However, tumor targeting of mRNA therapeutics is still a challenge, since, in addition to delivery of the cargo to the tumor, specifics of the targeted cell type as well as its interplay with the tumor microenvironment are crucial for successful intervention. This study investigated lipoplex nanoparticle-mediated mRNA delivery to spheroid cell culture models of melanoma. Insights into cell-type specific targeting, non-cell-autonomous effects, and penetration capacity in tumor and stroma cells of the mRNA lipoplex nanoparticles were obtained. It was shown that both coculture of different cell types as well as three-dimensional cell growth characteristics can modulate distribution and transfection efficiency of mRNA lipoplex formulations. The results demonstrate that three-dimensional coculture spheroids can provide a valuable surplus of information in comparison to adherent cells. Thus, they may represent in vitro models with enhanced predictivity for the in vivo activity of cancer nanotherapeutics.


Subject(s)
Melanoma , Nanoparticles , Coculture Techniques , Humans , Melanoma/therapy , Nanoparticles/therapeutic use , RNA , RNA, Messenger/genetics , Tumor Microenvironment
4.
Int J Mol Sci ; 23(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1753507

ABSTRACT

CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.


Subject(s)
Autoimmune Diseases , COVID-19 , HIV Infections , Neoplasms , Virus Diseases , CD28 Antigens , CD8-Positive T-Lymphocytes , Cellular Senescence , HIV Infections/drug therapy , Humans , SARS-CoV-2 , Tumor Microenvironment
5.
Nat Cell Biol ; 23(12): 1240-1254, 2021 12.
Article in English | MEDLINE | ID: covidwho-1699219

ABSTRACT

Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.


Subject(s)
Extracellular Vesicles/metabolism , MicroRNAs/metabolism , Nanoparticles/metabolism , Alzheimer Disease/pathology , Angiotensin-Converting Enzyme 2/metabolism , Biological Transport/physiology , Biomarkers/metabolism , COVID-19/pathology , Cardiovascular Diseases/pathology , Cell Communication/physiology , Cell Line, Tumor , HeLa Cells , Humans , Lactic Acid/metabolism , MicroRNAs/genetics , Nanoparticles/classification , Neoplasms/pathology , Tumor Microenvironment
6.
Hum Vaccin Immunother ; 18(1): 2024416, 2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-1672019

ABSTRACT

After one year of absence, the 18th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Europe's cancer immunotherapy meeting, took place virtually from 10 to 12 May 2021. Over 850 academic and clinical professionals from 30 countries met to discuss the recent advancements in cancer immunotherapy and the current progress in COVID19-related research. This meeting report summarizes the highlights of CIMT2021.


Subject(s)
COVID-19 , Neoplasms , Humans , Immunotherapy , Neoplasms/therapy , Tumor Microenvironment
7.
Gastroenterology ; 161(3): 785-791, 2021 09.
Article in English | MEDLINE | ID: covidwho-1626143

ABSTRACT

Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase in incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving the outcome of patients. On the 4th and 5th of February 2021, three German pancreatic cancer research centers, the Clinical Research Unit 5002 from Göttingen, the Collaborative Research Center 1321 from Munich, and Clinical Research Unit 325 from Marburg organized the 1st Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting in order to foster scientific exchange. This report summarizes current research and proceedings presented during that meeting.


Subject(s)
Biomedical Research/trends , Pancreatic Neoplasms , Animals , Biomarkers, Tumor/genetics , COVID-19 , Cell Lineage , Diffusion of Innovation , Genetic Predisposition to Disease , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Tumor Microenvironment , Videoconferencing
8.
Cells ; 10(11)2021 11 04.
Article in English | MEDLINE | ID: covidwho-1533814

ABSTRACT

Lung cancer organoid (LCO) is a novel model of lung cancer that facilitates drug screening. However, the success rate of LCOs varies from 7% to 87%, and the culture medium compositions are markedly different. Airway organoid media can be used for LCO cultures, but this promotes the overgrowth of normal cell organoids especially in LCOs from intrapulmonary lesions. Several modified media are specifically utilized for promoting the cancer cell's growth. For culturing high-purity LCOs, cancer cells from metastatic lesions and malignant effusions are used. Recently, single-cell RNA sequencing has identified previously unknown cell populations in the lungs and lung cancer. This sequencing technology can be used to validate whether the LCO recapitulates the heterogeneity and functional hierarchy of the primary tumor. Several groups have attempted to culture LCOs with mesenchymal cells and immune cells to recapitulate the tumor microenvironment. Disease modeling using LCO provides novel insight into the pathophysiology of lung cancer and enables high-throughput screening for drug discovery and prognosis prediction. An LCO model would help to identify new concepts as a basis for lung cancer targeting by discovering innovative therapeutic targets.


Subject(s)
Lung Neoplasms/pathology , Organoids/pathology , Animals , Clinical Trials as Topic , Disease Models, Animal , Humans , Reproducibility of Results , Tumor Microenvironment
9.
Eur J Cancer ; 160: 150-174, 2022 01.
Article in English | MEDLINE | ID: covidwho-1525772

ABSTRACT

The ability to exploit the immune system as a weapon against cancer has revolutionised the treatment of cancer patients, especially through immune checkpoint inhibitors (ICIs). However, ICIs demonstrated a modest benefit in treating breast cancer (BC), with the exception of certain subsets of triple-negative BCs. An immune-suppressive tumour microenvironment (TME), typically present in BC, is an important factor in the poor response to immunotherapy. After almost two decades of poor clinical trial results, cancer vaccines (CVs), an active immunotherapy, have come back in the spotlight because of some technological advancements, ultimately boosted by coronavirus disease 2019 pandemic. In particular, neoantigens are emerging as the preferred targets for CVs, with gene-based and viral vector-based platforms in development. Moreover, lipid nanoparticles proved to be immunogenic and efficient delivery vehicles. Past clinical trials investigating CVs focused especially on the metastatic disease, where the TME is more likely compromised by inhibitory mechanisms. In this sense, favouring the use of CVs as monotherapy in premalignant or in the adjuvant setting and establishing combination treatments (i.e. CV plus ICI) in late-stage disease are promising strategies. This review provides a full overview of the past and current breast cancer vaccine landscape.


Subject(s)
Breast Neoplasms/prevention & control , Cancer Vaccines/therapeutic use , Tumor Microenvironment , Animals , Breast Neoplasms/immunology , Female , Humans
10.
Int J Biol Sci ; 17(4): 1079-1087, 2021.
Article in English | MEDLINE | ID: covidwho-1524445

ABSTRACT

Fibrinogen-associated protein (FREP) family is a family of proteins with a fibrin domain at the carboxyl terminus. Recent investigations illustrated that two members of FREP family, fibrinogen-like protein-1 (FGL1) and fibrinogen-like protein-2 (FGL2), play crucial roles in cancer by regulating the proliferation, invasion, and migration of tumor cells, or regulating the functions of immune cells in tumor microenvironment. Meanwhile, they are potential targets for medical intervention of tumor development. In this review, we discussed the structure, and the roles of FGL1 and FGL2 in tumors, especially the roles in regulating immune cell functions.


Subject(s)
Fibrinogen/metabolism , Neoplasms/metabolism , Tumor Microenvironment/immunology , Animals , Humans , Immunotherapy , Molecular Targeted Therapy , Neoplasms/immunology , Neoplasms/therapy , Signal Transduction
11.
Theranostics ; 11(18): 9054-9088, 2021.
Article in English | MEDLINE | ID: covidwho-1524532

ABSTRACT

In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.


Subject(s)
Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Precision Medicine/methods , Humans , Neoplasms/therapy , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/metabolism , Reactive Oxygen Species , Theranostic Nanomedicine/methods , Tumor Microenvironment/drug effects
12.
Adv Drug Deliv Rev ; 181: 114033, 2022 02.
Article in English | MEDLINE | ID: covidwho-1520626

ABSTRACT

Neurosurgery as one of the most technologically demanding medical fields rapidly adapts the newest developments from multiple scientific disciplines for treating brain tumors. Despite half a century of clinical trials, survival for brain primary tumors such as glioblastoma (GBM), the most common primary brain cancer, or rare ones including primary central nervous system lymphoma (PCNSL), is dismal. Cancer therapy and research have currently shifted toward targeted approaches, and personalized therapies. The orchestration of novel and effective blood-brain barrier (BBB) drug delivery approaches, targeting of cancer cells and regulating tumor microenvironment including the immune system are the key themes of this review. As the global pandemic due to SARS-CoV-2 virus continues, neurosurgery and neuro-oncology must wrestle with the issues related to treatment-related immune dysfunction. The selection of chemotherapeutic treatments, even rare cases of hypersensitivity reactions (HSRs) that occur among immunocompromised people, and number of vaccinations they have to get are emerging as a new chapter for modern Nano neurosurgery.


Subject(s)
Brain Neoplasms/surgery , COVID-19/surgery , Neurosurgery/methods , Animals , Blood-Brain Barrier/surgery , Glioblastoma/surgery , Humans , Nanotechnology/methods , Pandemics/statistics & numerical data , Tumor Microenvironment/physiology
13.
Cells ; 10(10)2021 10 09.
Article in English | MEDLINE | ID: covidwho-1480599

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) constitute a plastic and heterogeneous cell population among immune cells within the tumour microenvironment (TME) that support cancer progression and resistance to therapy. During tumour progression, cancer cells modify their metabolism to sustain an increased energy demand to cope with uncontrolled cell proliferation and differentiation. This metabolic reprogramming of cancer establishes competition for nutrients between tumour cells and leukocytes and most importantly, among tumour-infiltrating immune cells. Thus, MDSCs that have emerged as one of the most decisive immune regulators of TME exhibit an increase in glycolysis and fatty acid metabolism and also an upregulation of enzymes that catabolise essential metabolites. This complex metabolic network is not only crucial for MDSC survival and accumulation in the TME but also for enhancing immunosuppressive functions toward immune effectors. In this review, we discuss recent progress in the field of MDSC-associated metabolic pathways that could facilitate therapeutic targeting of these cells during cancer progression.


Subject(s)
Metabolic Networks and Pathways , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Tumor Microenvironment/immunology , Animals , Humans , Molecular Targeted Therapy , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/therapy
14.
Cytokine Growth Factor Rev ; 63: 78-89, 2022 02.
Article in English | MEDLINE | ID: covidwho-1474466

ABSTRACT

The Covid-19 pandemic has spread rapidly across the globe, resulting in more than 3 million deaths worldwide. The symptoms of Covid-19 are usually mild and non-specific, however in some cases patients may develop acute respiratory distress syndrome (ARDS) and systemic inflammation. Individuals with inflammatory or immunocompromising illnesses, such as cancer, are more susceptible to develop ARDS and have higher rates of mortality. This is mediated through an initial hyperstimulated immune response which results in elevated levels of pro-inflammatory cytokines and a subsequent cytokine storm. This potentiates positive feedback loops which are unable to be balanced by anti-inflammatory mediators. Therefore, elevated levels of IL-1ß, as a result of NLRP3 inflammasome activation, as well as IL-6 and TNF-α amongst many others, contribute to the progression of various cancer types. Furthermore, Covid-19 progression is associated with the depletion of CD8+ and CD4+ T cells, B cell and natural killer cell numbers. Collectively, a Covid-19-dependent pro-inflammatory profile and immune suppression promotes the optimal microenvironment for tumourigenesis, initiation and immune evasion of malignant cells, tumour progression and metastasis as well as cancer recurrence. There are, however, therapeutic windows of opportunity that may combat both Covid-19 and cancer to improve patient outcomes.


Subject(s)
COVID-19 , Neoplasms , Cytokine Release Syndrome , Cytokines , Humans , Pandemics , SARS-CoV-2 , Tumor Microenvironment
15.
J Immunother Cancer ; 9(9)2021 09.
Article in English | MEDLINE | ID: covidwho-1403102

ABSTRACT

BACKGROUND: The clinical benefit of immune checkpoint blockade (ICB) therapy is often limited by the lack of pre-existing CD8+ T cells infiltrating the tumor. In principle, CD8+ T-cell infiltration could be promoted by therapeutic vaccination. However, this remains challenging given the paucity of vaccine platforms able to induce the strong cytotoxic CD8+ T-cell response required to reject tumors. A therapeutic cancer vaccine that induces a robust cytotoxic CD8+ T-cell response against shared tumor antigens and can be combined with ICB could improve the outcome of cancer immunotherapy. METHODS: Here, we developed a heterologous prime-boost vaccine based on a chimpanzee adenovirus (ChAdOx1) and a modified vaccinia Ankara (MVA) encoding MAGE-type antigens, which are tumor-specific shared antigens expressed in different tumor types. The mouse MAGE-type antigen P1A was used as a surrogate to study the efficacy of the vaccine in combination with ICB in murine tumor models expressing the P1A antigen. To characterize the vaccine-induced immune response, we performed flow cytometry and transcriptomic analyses. RESULTS: The ChAdOx1/MVA vaccine displayed strong immunogenicity with potent induction of CD8+ T cells. When combined with anti-Programmed Cell Death Protein 1 (PD-1), the vaccine induced superior tumor clearance and survival in murine tumor models expressing P1A compared with anti-PD-1 alone. Remarkably, ChAdOx1/MVA P1A vaccination promoted CD8+ T-cell infiltration in the tumors, and drove inflammation in the tumor microenvironment, turning 'cold' tumors into 'hot' tumors. Single-cell transcriptomic analysis of the P1A-specific CD8+ T cells revealed an expanded population of stem-like T cells in the spleen after the combination treatment as compared with vaccine alone, and a reduced PD-1 expression in the tumor CD8+ T cells. CONCLUSIONS: These findings highlight the synergistic potency of ChAdOx1/MVA MAGE vaccines combined with anti-PD-1 for cancer therapy, and establish the foundation for clinical translation of this approach. A clinical trial of ChadOx1/MVA MAGE-A3/NY-ESO-1 combined with anti-PD-1 will commence shortly.


Subject(s)
Antigens, Heterophile/drug effects , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Neoplasms/drug therapy , Vaccination/methods , Animals , Female , Humans , Immune Checkpoint Inhibitors/pharmacology , Mice , Tumor Microenvironment
16.
Int J Mol Sci ; 22(9)2021 Apr 27.
Article in English | MEDLINE | ID: covidwho-1390655

ABSTRACT

The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. The diverse activities of thrombospondin-1 to regulate autophagy, senescence, stem cell maintenance, extracellular vesicle function, and metabolic responses to ischemic and genotoxic stress are mediated by several cell surface receptors and by regulating the functions of several secreted proteins. This review highlights progress in understanding thrombospondin-1 functions in cancer and the challenges that remain in harnessing its therapeutic potential.


Subject(s)
Neoplasms , Thrombospondin 1/physiology , Tumor Microenvironment/physiology , Animals , Cell Adhesion , Cell Movement , Humans , Integrins/metabolism , Mice , Neoplasms/blood supply , Neoplasms/immunology , Neoplasms/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Physiologic/genetics , T-Lymphocytes/immunology , Thrombospondin 1/genetics , Thrombospondin 1/metabolism
17.
J Mammary Gland Biol Neoplasia ; 26(3): 221-226, 2021 09.
Article in English | MEDLINE | ID: covidwho-1375665

ABSTRACT

The twelfth annual workshop of the European Network for Breast Development and Cancer focused on methods in mammary gland biology and breast cancer, was scheduled to take place on March 26-28, 2020, in Weggis, Switzerland. Due to the COVID-19 pandemic, the meeting was rescheduled twice and eventually happened as a virtual meeting on April 22 and 23, 2021. The main topics of the meeting were branching and development of the mammary gland, tumor microenvironment, circulating tumor cells, tumor dormancy and breast cancer metastasis. Novel and unpublished findings related to these topics were presented, with a particular focus on the methods used to obtain them. Virtual poster sessions were a success, with many constructive and fruitful interactions between researchers and covered many areas of mammary gland biology and breast cancer.


Subject(s)
Biomedical Research/methods , Breast Neoplasms/pathology , Mammary Glands, Human/pathology , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Combined Modality Therapy , Europe , Female , Humans , Mammary Glands, Human/growth & development , Mammary Glands, Human/metabolism , Neoplasm Metastasis , Neoplasm Staging , Neoplastic Cells, Circulating , Prognosis , Tumor Microenvironment
18.
Front Immunol ; 12: 679425, 2021.
Article in English | MEDLINE | ID: covidwho-1344264

ABSTRACT

Gliomas are the most common primary brain tumors in adults. Despite the fact that they are relatively rare, they cause significant morbidity and mortality. High-grade gliomas or glioblastomas are rapidly progressing tumors with a very poor prognosis. The presence of an intrinsic immune system in the central nervous system is now more accepted. During the last decade, there has been no major progress in glioma therapy. The lack of effective treatment for gliomas can be explained by the strategies that cancer cells use to escape the immune system. This being said, immunotherapy, which involves blockade of immune checkpoint inhibitors, has improved patients' survival in different cancer types. This novel cancer therapy appears to be one of the most promising approaches. In the present study, we will start with a review of the general concept of immune response within the brain and glioma microenvironment. Then, we will try to decipher the role of various immune checkpoint inhibitors within the glioma microenvironment. Finally, we will discuss some promising therapeutic pathways, including immune checkpoint blockade and the body's effective anti-glioma immune response.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Glioma/drug therapy , Glioma/pathology , Immune Checkpoint Inhibitors/therapeutic use , Tumor Microenvironment/drug effects , Biomarkers, Tumor , Brain/drug effects , Brain/immunology , Brain/metabolism , Brain/pathology , Brain Neoplasms/etiology , Brain Neoplasms/mortality , Disease Susceptibility , Glioma/etiology , Glioma/mortality , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Proteins/genetics , Immune Checkpoint Proteins/metabolism , Molecular Targeted Therapy , Prognosis , Treatment Outcome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
19.
J Immunol ; 207(2): 720-734, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1311404

ABSTRACT

Most shared resource flow cytometry facilities do not permit analysis of radioactive samples. We are investigating low-dose molecular targeted radionuclide therapy (MTRT) as an immunomodulator in combination with in situ tumor vaccines and need to analyze radioactive samples from MTRT-treated mice using flow cytometry. Further, the sudden shutdown of core facilities in response to the COVID-19 pandemic has created an unprecedented work stoppage. In these and other research settings, a robust and reliable means of cryopreservation of immune samples is required. We evaluated different fixation and cryopreservation protocols of disaggregated tumor cells with the aim of identifying a protocol for subsequent flow cytometry of the thawed sample, which most accurately reflects the flow cytometric analysis of the tumor immune microenvironment of a freshly disaggregated and analyzed sample. Cohorts of C57BL/6 mice bearing B78 melanoma tumors were evaluated using dual lymphoid and myeloid immunophenotyping panels involving fixation and cryopreservation at three distinct points during the workflow. Results demonstrate that freezing samples after all staining and fixation are completed most accurately matches the results from noncryopreserved equivalent samples. We observed that cryopreservation of living, unfixed cells introduces a nonuniform alteration to PD1 expression. We confirm the utility of our cryopreservation protocol by comparing tumors treated with in situ tumor vaccines, analyzing both fresh and cryopreserved tumor samples with similar results. Last, we use this cryopreservation protocol with radioactive specimens to demonstrate potentially beneficial effector cell changes to the tumor immune microenvironment following administration of a novel MTRT in a dose- and time-dependent manner.


Subject(s)
Cryopreservation/methods , Flow Cytometry/methods , Leukocytes, Mononuclear/immunology , Melanoma, Experimental/pathology , Myeloid Cells/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Immunophenotyping/methods , Mice , Mice, Inbred C57BL , Natural Killer T-Cells/immunology , Pandemics , Signal Transduction/immunology , Tumor Microenvironment/immunology
20.
Med Oncol ; 38(8): 90, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1287464

ABSTRACT

During the COVID-19 pandemic, it is important to assure the safety and management of cancer patients. Despite preliminary studies revealed that patients with cancer are more susceptible to infection and have poorer prognosis than other infected patients without cancer, mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. So, we have some comments about the pathogenesis attributed to the COVID-19 disease and cancer relationship and determination of subgroups in this and oncoming studies. Variable effects of anticancer treatments on the patient's immune system are yet to be elucidated. On the other hand, the effect of SARS-CoV-2 virus on tumor microenvironment or immune responses in cancer is not yet fully proven. Very recently, Challenor and her colleague reported a case with classical Hodgkin lymphoma with stage IIIs disease, which went into remission without corticosteroid or immunochemotherapy. They assumed that the putative mechanisms of action include cross-reactivity of pathogen-specific T cells with tumor antigens and natural killer cell activation by inflammatory cytokines produced in response to infection. During the course of COVID-19 disease, immune checkpoint blockade effect might be induced naturally.


Subject(s)
COVID-19/immunology , Neoplasms/immunology , SARS-CoV-2/immunology , Cross Reactions , Cytokines/immunology , Humans , Immune Checkpoint Inhibitors/immunology , Lymphocyte Activation , T-Lymphocytes/immunology , Tumor Microenvironment/immunology
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