scholarly journals Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Heng Zhou ◽  
Pengfei Yang ◽  
Haining Li ◽  
Liying Zhang ◽  
Jin Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Ion Beams ◽  
Carbon Ion Radiotherapy ◽  
Myeloid Derived Suppressor Cells ◽  
Carbon Ion ◽  
Immune Contexture

AbstractNumerous studies have shown that carbon ion radiotherapy (CIRT) induces anti-cancer immune responses in melanoma patients, yet the mechanism remains elusive. The abundance of myeloid-derived suppressor cells (MDSC) in the tumour microenvironment is associated with therapeutic efficacy and disease outcome. This study analysed the changes in the immune contexture in response to the carbon ion treatment. The murine melanoma B16, MelanA, and S91 tumour models were established in syngeneic immunocompetent mice. Then, the tumours were irradiated with carbon ion beams, and flow cytometry was utilised to observe the immune contexture changes in the bone marrow, peripheral blood, spleen, and tumours. The immune infiltrates in the tumour tissues were further assessed using haematoxylin/eosin staining and immunohistochemistry. The immunoblot detected the expression of proteins associated with the JAK/STAT signalling pathway. The secretion of immune-related cytokines was examined using ELISA. Compared to conventional radiotherapy, particle beams have distinct advantages in cancer therapy. Here, the use of carbon ion beams (5 GyE) for melanoma-bearing mice was found to reduce the population of MDSC in the bone marrow, peripheral blood, and spleen of the animals via a JAK2/STAT3-dependent mechanism. The percentage of CD3+, CD4+, CD8+ T cells, macrophages, and natural killer cells increased after radiation, resulting in reduced tumour growth and prolonged overall survival in the three different mouse models of melanoma. This study, therefore, substantiated that CIRT boosts anti-tumour immune responses via the inhibition of MDSC.

Absolute Monocytosis At Diagnosis Is Associated with Poor Survival in Diffuse Large B-Cell Lymphoma -Possibly Related to Increase in Monocytic-Myeloid Derived Suppressor Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2641-2641
Author(s):  
Tamar Tadmor ◽  
Rona Fell ◽  
Aaron Polliack ◽  
Dina Attias
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Immune Response ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Poor Survival

Abstract Abstract 2641 Background: monocytes and macrophages play a role in promoting angiogenesis and suppression of the anti-tumor immune response. Monocytic-myeloid derived suppressor cells (M-MDSCs) are a subpopulation of immature myeloid cells which have immune-suppressive function and play a role in cancer tolerance. Some patients with malignant lymphoma exhibit peripheral blood monocytosis (PBM) at diagnosis but its exact prevalence is not known. Aim: Recently we encountered PBM in a few patients with DLBCL who had a rapidly progressive fatal course. This observation coupled with emerging data on the role of M-MDSCs is in the tumor microenvironment, led us to undertake a retrospective study to determine prevalence of PBM and its possible prognostic significance in DLBCL. In a proportion of these patients we also quantitated the M-MDSCs pool in the peripheral blood using flow cytometry in an attempt to assess possible changes in this subpopulation of monocytic cells in DLBCL. Material and methods: Clinical and laboratory data from medical records of 91 newly diagnosed patients with DLBCL seen at our institute during 1996–2010, were evaluated for the presence of absolute PBM> 1000 cells/mm3, at diagnosis and for possible correlations with other prognostic factors including age, stage, gender, B symptoms, extra nodal involvement, serum LDH and CRP levels, bone marrow (BM) involvement and IPI score. A Cox proportional hazards regression model was used to determine significance of the prognostic factors in a multivariate analysis. In the last 23 consecutive patients flow-cytometry analysis peripheral blood cells was also performed using surface staining for CD45+CD14+ HLA DR−/LOW to define the proportion of M-MDSCs compared to 15 healthy volunteers. Statistical analysis of was done using student T-TEST. Results: The median age of the entire patient cohort was 66 years (21–87); median follow up was 30 months: (1–332 months) and 57 % were men. All patients received CHOP or R-CHOP. PBM was found in 18.3% at diagnosis. In the multivariate analysis (Cox model), only PBM, bone marrow involvement and IPI score were found to be independent prognostic factors for overall survival (OS) while age and LDH weren't (Table). Blood samples collected at diagnosis from 23 patients showed increased numbers of M- MDSCs compared to healthy volunteers (9.59% range: 5.6–19 % and, 5.44% range 4.8–7.7 % respectively p<0.05).Levels of MDSCs decreased to within normal limits when performed 3 month following chemotherapy in patient in CR (5.76% range: 5.1–7.2 %). In conclusion: These results show that PBM is an independent factor for predicting poor survival in patients with DLCL and was as significant a risk factor as IPI score. This simple routine laboratory test can be utilized in daily practice as another indicator of poor outcome in DLBCL. The findings provide further support for the functional role of monocytes in the immune response in DLBCL. Furthermore, the consistent finding of significantly increased numbers of M-MDSC in the peripheral blood in these patients suggests that this subpopulation of immunosuppressive monocytes may contribute to the decreased tumor surveillance seen in DLBCL and may help to explain why absolute PBM is associated with poor outcome in these patients. Studies on their biological role as a marker of disease activity in DLBCL are in progress. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Carbon ion radiotherapy for recurrent calf myxoid liposarcoma: a case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110097
Author(s):  
Xiaojun Li ◽  
Yanshan Zhang ◽  
Yancheng Ye ◽  
Ying Qi ◽  
Chunlan Feng ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Myxoid Liposarcoma ◽  
Ion Beams ◽  
Carbon Ion Radiotherapy ◽  
Irradiation Damage ◽  
Radiation Dermatitis ◽  
Complete Disappearance ◽  
Carbon Ion ◽  
The Right

Liposarcoma (LPS) is the most common soft tissue sarcoma. Myxoid LPS (MLPS) is the second most common subtype of LPS and accounts for 25% to 50% of all LPSs. Like most other soft tissue sarcomas, the mainstay of treatment for LPS is inevitably surgery. Multidisciplinary approaches, including surgery, chemotherapy, and radiotherapy, have been successful in the treatment of LPS during the last three decades. Even so, recurrence of LPS remains challenging. Carbon ion beams produce increased energy deposition at the end of their range to form a Bragg peak while minimizing irradiation damage to surrounding tissues, which facilitates more precise dosage and localization than that achieved with photon beams. Furthermore, carbon ion beams have high relative biologic effectiveness. We herein describe a patient who developed recurrent MLPS in the right calf after two surgeries and underwent carbon ion radiotherapy (CIRT), achieving complete disappearance of the tumor. The patient developed Grade 1 radiation dermatitis 30 days after CIRT, but no other acute toxicities were observed. The tumor had completely disappeared by 120 days after CIRT, and the patient remained disease-free for 27 months after CIRT. The CARE guidelines were followed in the reporting of this case.

scholarly journals Expansion of Functional Myeloid-Derived Suppressor Cells in Controlled Human Malaria Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos Lamsfus Calle ◽  
Rolf Fendel ◽  
Anurag Singh ◽  
Thomas L. Richie ◽  
Stephen L. Hoffman ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Malaria Infection ◽  
Malaria Vaccine ◽  
Suppressor Cells ◽  
T Cell Proliferation ◽  
Myeloid Derived Suppressor Cells ◽  
Controlled Human Malaria Infection

Malaria can cause life-threatening complications which are often associated with inflammatory reactions. More subtle, but also contributing to the burden of disease are chronic, often subclinical infections, which result in conditions like anemia and immunologic hyporesponsiveness. Although very frequent, such infections are difficult to study in endemic regions because of interaction with concurrent infections and immune responses. In particular, knowledge about mechanisms of malaria-induced immunosuppression is scarce. We measured circulating immune cells by cytometry in healthy, malaria-naïve, adult volunteers undergoing controlled human malaria infection (CHMI) with a focus on potentially immunosuppressive cells. Infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) were inoculated during two independent studies to assess malaria vaccine efficacy. Volunteers were followed daily until parasites were detected in the circulation by RT-qPCR. This allowed us to analyze immune responses during pre-patency and at very low parasite densities in malaria-naïve healthy adults. We observed a consistent increase in circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in volunteers who developed P. falciparum blood stage parasitemia. The increase was independent of preceding vaccination with a pre-erythrocytic malaria vaccine. PMN-MDSC were functional, they suppressed CD4+ and CD8+ T cell proliferation as shown by ex-vivo co-cultivation with stimulated T cells. PMN-MDSC reduced T cell proliferation upon stimulation by about 50%. Interestingly, high circulating PMN-MDSC numbers were associated with lymphocytopenia. The number of circulating regulatory T cells (Treg) and monocytic MDSC (M-MDSC) showed no significant parasitemia-dependent variation. These results highlight PMN-MDSC in the peripheral circulation as an early indicator of infection during malaria. They suppress CD4+ and CD8+ T cell proliferation in vitro. Their contribution to immunosuppression in vivo in subclinical and uncomplicated malaria will be the subject of further research. Pre-emptive antimalarial pre-treatment of vaccinees to reverse malaria-associated PMN-MDSC immunosuppression could improve vaccine response in exposed individuals.

scholarly journals Granulocytic Myeloid-Derived Suppressor Cells Aggravate Tuberculosis Caused by Hypervirulent Mycobacteria

2020 ◽  
Author(s):  
Caio César Barbosa Bomfim ◽  
Eduardo Pinheiro Amaral ◽  
Igor Santiago-Carvalho ◽  
Gislane Almeida Santos ◽  
Érika Machado Salles ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cell Function ◽  
Pulmonary Inflammation ◽  
Bacterial Load ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Partial Recovery ◽  
Myeloid Derived Suppressor Cells

Abstract Background The role of myeloid-derived suppressor cells (MDSCs) in severe tuberculosis patients who suffer from uncontrolled pulmonary inflammation caused by hypervirulent mycobacterial infection remains unclear. Methods This issue was addressed using C57BL/6 mice infected with highly virulent Mycobacterium bovis strain MP287/03. Results CD11b +GR1 int population increased in the bone marrow, blood and lungs during advanced disease. Pulmonary CD11b +GR1 int (Ly6G intLy6C int) cells showed granularity similar to neutrophils and expressed immature myeloid cell markers. These immature neutrophils harbored intracellular bacilli and were preferentially located in the alveoli. T cell suppression occurred concomitantly with CD11b +GR1 int cell accumulation in the lungs. Furthermore, lung and bone-marrow GR1 + cells suppressed both T cell proliferation and IFN-γ production in vitro. Anti-GR1 therapy given when MDSCs infiltrated the lungs prevented expansion and fusion of primary pulmonary lesions and the development of intragranulomatous caseous necrosis, along with increased mouse survival and partial recovery of T cell function. Lung bacterial load was reduced by anti-GR1 treatment, but mycobacteria released from the depleted cells proliferated extracellularly in the alveoli, forming cords and clumps. Conclusions Granulocytic MDSCs massively infiltrate the lungs during infection with hypervirulent mycobacteria, promoting bacterial growth and the development of inflammatory and necrotic lesions, and are promising targets for host-directed therapies.

scholarly journals Myeloid-derived suppressor cells in hematological malignancies: friends or foes

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Meng Lv ◽  
Ke Wang ◽  
Xiao-jun Huang
Keyword(s):  
Multiple Myeloma ◽  
Immune Responses ◽  
Tumor Immunology ◽  
Hematological Malignancies ◽  
Inflammatory Diseases ◽  
Suppressor Cells ◽  
Multiple Roles ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Immature Myeloid Cells

Abstract Myeloid-derived suppressor cells (MDSCs) are newly identified immature myeloid cells that are characterized by the ability to suppress immune responses and expand during cancer, infection, and inflammatory diseases. Although MDSCs have attracted a lot of attention in the field of tumor immunology in recent years, little is known about their multiple roles in hematological malignancies as opposed to their roles in solid tumors. This review will help researchers better understand the various characteristics and functions of MDSCs, as well as the potential therapeutic applications of MDSCs in hematological malignancies, including lymphoma, multiple myeloma, leukemia, and hematopoietic stem cell transplantation.

scholarly journals Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 561 ◽  
Author(s):  
Andrew M. K. Law ◽  
Fatima Valdes-Mora ◽  
David Gallego-Ortega
Keyword(s):  
Cancer Progression ◽  
Therapeutic Target ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Myeloid Derived Suppressor Cells ◽  
Cancer Treatments ◽  
Patient Response

The emergence of immunotherapy has been an astounding breakthrough in cancer treatments. In particular, immune checkpoint inhibitors, targeting PD-1 and CTLA-4, have shown remarkable therapeutic outcomes. However, response rates from immunotherapy have been reported to be varied, with some having pronounced success and others with minimal to no clinical benefit. An important aspect associated with this discrepancy in patient response is the immune-suppressive effects elicited by the tumour microenvironment (TME). Immune suppression plays a pivotal role in regulating cancer progression, metastasis, and reducing immunotherapy success. Most notably, myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have potent mechanisms to inhibit T-cell and NK-cell activity to promote tumour growth, development of the pre-metastatic niche, and contribute to resistance to immunotherapy. Accumulating research indicates that MDSC can be a therapeutic target to alleviate their pro-tumourigenic functions and immunosuppressive activities to bolster the efficacy of checkpoint inhibitors. In this review, we provide an overview of the general immunotherapeutic approaches and discuss the characterisation, expansion, and activities of MDSCs with the current treatments used to target them either as a single therapeutic target or synergistically in combination with immunotherapy.

scholarly journals Mesenchymal Stem Cells and Myeloid Derived Suppressor Cells: Common Traits in Immune Regulation

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Irina Lyadova Vladimirovna ◽  
Ekaterina Sosunova ◽  
Alexander Nikolaev ◽  
Tatiana Nenasheva
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Immune Regulation ◽  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Regulatory Cells ◽  
B Regulatory Cells ◽  
Immature Cells

To protect host against immune-mediated damage, immune responses are tightly regulated. The regulation of immune responses is mediated by various populations of mature immune cells, such as T regulatory cells and B regulatory cells, but also by immature cells of different origins. In this review, we discuss regulatory properties and mechanisms whereby two distinct populations of immature cells, mesenchymal stem cells, and myeloid derived suppressor cells mediate immune regulation, focusing on their similarities, discrepancies, and potential clinical applications.

Immature myeloid Gr-1+ CD11b+ cells from lipopolysaccharide-immunosuppressed mice acquire inhibitory activity in the bone marrow and migrate to lymph nodes to exert their suppressive function

2016 ◽  
Vol 130 (4) ◽  
pp. 259-271 ◽  
Author(s):  
Veronica I. Landoni ◽  
Daiana Martire-Greco ◽  
Nahuel Rodriguez-Rodrigues ◽  
Paula Chiarella ◽  
Pablo Schierloh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Lymph Nodes ◽  
Inhibitory Activity ◽  
Suppressor Cells ◽  
T Cell Responses ◽  
Myeloid Derived Suppressor Cells ◽  
Suppressive Function ◽  
Cell Responses ◽  
Immunosuppressed Mice

LPS-induced immunosuppression, mimicking the state observed in patients with late sepsis, induced in bone marrow a population of myeloid-derived suppressor cells (Gr-1+ CD11b+) with the ability to inhibit T-cell responses and migrate to lymph nodes to exert their suppressive function.

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