scholarly journals Resistance to Immune Checkpoint Inhibitors Secondary to Myeloid-Derived Suppressor Cells: A New Therapeutic Targeting of Haematological Malignancies

2021 ◽  
Vol 10 (9) ◽  
pp. 1919
Author(s):  
Alejandro Olivares-Hernández ◽  
Luis Figuero-Pérez ◽  
Eduardo Terán-Brage ◽  
Álvaro López-Gutiérrez ◽  
Álvaro Tamayo Velasco ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
Routine Clinical Practice ◽  
Myeloid Derived Suppressor Cells ◽  
Haematological Malignancies ◽  
Therapeutic Targeting ◽  
Haematological Neoplasms ◽  
Different Levels

Myeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors (ICIs). Currently, multiple studies at the preclinical and clinical levels seek to use this cell population for the treatment of different haematological neoplasms, together with ICIs. This review addresses the different points in ongoing studies of MDSCs and ICIs in haematological malignancies and their future significance in routine clinical practice.

EXTRATUMOR MICROENVIRONMENT IN RENAL CELL CARCINOMA

2021 ◽  
Vol 2 (4) ◽  
pp. 5-12
Author(s):  
Mirzagaleb Tillyashaykhov ◽  
◽  
Elena Boyko ◽  
Shakhnoza Jumaniyazova
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Animal Tumor

The review is focused on studying the immunosuppressive mechanisms acting in the microenvironment of renal cell carcinoma tumors. The report contains a collection of basic literature materials on the study of tumor growth factors that boost tumor cell proliferation and metastasis. The tumor microenvironment (TME) limits the immune surveillance of tumor-associated antigens and the effectiveness of immune checkpoint inhibitors. Although renal cell carcinoma is one of several tumor types sensitive to immune checkpoint inhibitors, the efficacy of these agents is likely to be limited by different tumor-infiltrating myeloid cells of bone marrow that make up the TME. Several strategies aimed at eliminating the onset of these cells in tumor tissue or neutralizing their immunosuppressive function have shown encouraging results in animal tumor models and clinical trials.Keywords: cytotoxic T lymphocytes (CTL), immune checkpoint inhibitor (ICI), tumor microenvironment (MEV), myeloid-derived suppressor cells (MDSC), regulatory T cells (Tregs), renal cell carcinoma (RCC), tumor-associated macrophages (TAM), vascular endothelial growth factor (VEGF)

scholarly journals Predictive Biomarkers for Outcomes of Immune Checkpoint Inhibitors (ICIs) in Melanoma: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6366
Author(s):  
Joosje C. Baltussen ◽  
Marij J. P. Welters ◽  
Elizabeth M. E. Verdegaal ◽  
Ellen Kapiteijn ◽  
Anne M. R. Schrader ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Suppressor Cells ◽  
Cochrane Library ◽  
Durable Response ◽  
Melanoma Patients

Immune checkpoint inhibitors (ICIs) have strongly improved the survival of melanoma patients. However, as durable response to ICIs are only seen in a minority, there is an unmet need to identify biomarkers that predict response. Therefore, we provide a systematic review that evaluates all biomarkers studied in association with outcomes of melanoma patients receiving ICIs. We searched Pubmed, COCHRANE Library, Embase, Emcare, and Web of Science for relevant articles that were published before June 2020 and studied blood, tumor, or fecal biomarkers that predicted response or survival in melanoma patients treated with ICIs. Of the 2536 identified reports, 177 were included in our review. Risk of bias was high in 40%, moderate in 50% and low in 10% of all studies. Biomarkers that correlated with response were myeloid-derived suppressor cells (MDSCs), circulating tumor cells (CTCs), CD8+ memory T-cells, T-cell receptor (TCR) diversity, tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), and a favorable gut microbiome. This review shows that biomarkers for ICIs in melanoma patients are widely studied, but heterogeneity between studies is high, average sample sizes are low, and validation is often lacking. Future studies are needed to further investigate the predictive utility of some promising candidate biomarkers.

CTLA4 and CD47 combinational therapy to extend survival in melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21025-e21025
Author(s):  
Anthony L. Schwartz ◽  
Pulak Nath ◽  
Elizabeth Lessey-Morillon ◽  
Lisa Ridnour ◽  
Michael Allgaeuer ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cell Activation ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Granzyme B ◽  
Suppressor Cells ◽  
Cell Infiltration

e21025 Background: Irradiation (IR) combined with chemotherapy is the post-surgical standard of care treatment for melanoma, but metastasis still results in high mortality rates. Immune checkpoint inhibitors such as cytotoxic T-lymphocyte antigen-4 (CTLA4) have proven effective for immunotherapy of melanoma. CTLA-4 is up-regulated post-T cell activation and blockade enhances tumor responses in immunocompetent rodents and humans. Trials suggest that combinations of immune checkpoint inhibitors are more efficacious than single agents, but tumors remain resistant. We are investigating CD47 blockade for the treatment of cancer. CD47 is frequently elevated in cancers and serves as an inhibitory receptor for thrombospondin-1 on immune cells in the tumor stroma. CD47 blockade on CD8 T or tumor cells significantly enhances immune-targeted tumor cell killing post-IR compared to IR alone. Here we explore the potential for antisense CD47 and anti-CTLA4 therapy alone or in combination with IR using a syngeneic mouse melanoma model. Methods: C57BL/6 mice were inoculated with 1x106B16F10 melanoma cells in the hind limb and treated with 10 Gy IR combined with CTLA4 blocking antibody, CD47 translational blocking morpholino, or the combination of CTLA4/CD47 therapies. Granzyme B along with CD4/CD8 T cell infiltration were examined in tumors. Histology was evaluated for CD3 and necrosis. Results: The combination of CD47/CTLA4 with IR significantly increased survival by 25% compared to IR/CTLA4 alone at 50 days. Granzyme B expression was significantly increased in IR mice with CTLA4/CD47 combination, which correlated with infiltration of CD8+ T cells and a concomitant decrease in Gr1+CD11b suppressor cells compared to controls. In non-IR tumors, histology revealed minimal necrosis, while all IR groups showed increased necrosis. Tumor IR in combination with CTLA4 or CD47 increased immune cell infiltration. However, the combination of IR with CTLA4/CD47 showed widespread necrosis. All groups treated with the CD47 exhibited focal hemorrhage, which was more extensive when combined with CTLA4. Conclusions: Results herein suggest IR combined CTLA4/CD47 checkpoint blockade provides a survival benefit by activating a beneficial adaptive immune response.

Safety and Efficacy of Immune Checkpoint Inhibitors in Children and Young Adults with Haematological Malignancies: Review and Future Perspectives

2021 ◽  
Vol 19 ◽  
Author(s):  
Eleni Tsotridou ◽  
Eleni Vasileiou ◽  
Elpis Mantadakis ◽  
Athanasios Tragiannidis
Keyword(s):  
Clinical Trials ◽  
Young Adults ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Safety Data ◽  
Case Series ◽  
Great Promise ◽  
Haematological Malignancies

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blockade of inhibitory receptors and have shown great promise in preclinical models and studies in the adult population. However, paediatric malignancies present unique features and so far, experience with these agents remains limited. In the current review we present an overview of efficacy and safety data from case reports, case series and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

scholarly journals Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueyan Li ◽  
Jiahui Zhong ◽  
Xue Deng ◽  
Xuan Guo ◽  
Yantong Lu ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Therapy Resistance ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Antitumor Efficacy ◽  
Myeloid Derived Suppressor Cells ◽  
Immature Myeloid Cells ◽  
Different Levels

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are activated under pathological conditions, such as cancer, or mature myeloid cells that are converted immune-suppressive cells via tumor-derived exosomes, and potently support the tumor processes at different levels. Currently, multiple studies have demonstrated that MDSCs induce immune checkpoint blockade (ICB) therapy resistance through their contribution to the immunosuppressive network in the tumor microenvironment. In addition, non-immunosuppressive mechanisms of MDSCs such as promotion of angiogenesis and induction of cancer stem cells also exert a powerful role in tumor progression. Thus, MDSCs are potential therapeutic targets to enhance the antitumor efficacy of ICB therapy in cases of multiple cancers. This review focuses on the tumor-promoting mechanism of MDSCs and provides an overview of current strategies that target MDSCs with the objective of enhancing the antitumor efficacy of ICB therapy.

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