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.

EXTH-08. STAT3 AT THE CROSSROADS OF INNATE IMMUNE ACTIVATION IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi164-vi165
Author(s):  
Christina von Roemeling ◽  
Lan Hoang-Minh ◽  
Bently Doonan ◽  
Chenglong Li ◽  
Duane Mitchell
Keyword(s):  
Immune Suppression ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Checkpoint Blockade ◽  
Tumor Bearing ◽  
Stat3 Inhibition

Abstract BACKGROUND Innate immune cells comprise the majority of the immune microenvironment in glioblastoma (GBM) tumors where they are chiefly thought to foster a hospitable environment for cancer cells by regulating immune suppression and driving resistance to immunotherapy. Of these, myeloid-derived suppressor cells (MDSCs) are regarded as one of the most potent contributors to immune suppression in GBM and thus have become a focus of targeted therapy. Signal transducer and activator of transcription 3 (STAT3) is a key phenotypic regulator of MDSCs. Therefore, we sought to examine if targeted STAT3 inhibition may augment the immunogenicity of these tumors. HYPOTHESIS: Targeted STAT3 inhibition reduces GBM tumor infiltration by MDSCs. METHODS Using syngeneic murine models of GBM, we performed pharmacological inhibition analyses using a specific small molecule inhibitor of STAT3, LLL12B. Circulating numbers of immune cells were assessed in tumor bearing animals with or without concomitant focal radiation. Treated tumors were examined for immune infiltrates, and additional phenotyping analyses were performed. Therapeutic responses to LLL12B alone and in combination with immune checkpoint blockade were evaluated. RESULTS STAT3 is activated in the bone marrow of tumor-bearing animals, preferentially by Gr-1 positive granulocytic myeloid cells. Increased circulating numbers of these cells were also detected. These observations were markedly enhanced in tumor-bearing animals following cranial irradiation. Therapeutic inhibition with LLL12B could mitigate these effects, indicating a dependency on STAT3. Within the tumor compartment, granulocytic myeloid cells that successfully infiltrated following treatment demonstrated a pro-inflammatory phenotype denoted by interferon-gamma expression. Improved survival was also observed following combination treatment with LLL12B and radiation or immune checkpoint blockade. CONCLUSIONS These findings advocate a critically important role for STAT3 in regulating granulocytic myeloid cell mobilization and trafficking to GBM tumors. It further illustrates the plasticity of these cells within these tumors, which may be useful in designing successful immunotherapeutic strategies.

scholarly journals Chemotherapy-induced recruitment of myeloid-derived suppressor cells abrogates efficacy of immune checkpoint blockade

JHEP Reports ◽  
2020 ◽  
pp. 100224
Author(s):  
Tsz Tung Kwong ◽  
Chi Hang Wong ◽  
Jing Ying Zhou ◽  
Alfred Sze Lok Cheng ◽  
Joseph Jao Yiu Sung ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Myeloid Derived Suppressor Cells

scholarly journals Immune checkpoint blockade in triple negative breast cancer influenced by B cells through myeloid-derived suppressor cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alyssa Vito ◽  
Omar Salem ◽  
Nader El-Sayes ◽  
Ian P. MacFawn ◽  
Ana L. Portillo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
B Cells ◽  
Rna Sequencing ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Myeloid Derived Suppressor Cells

AbstractTriple negative breast cancer holds a dismal clinical outcome and as such, patients routinely undergo aggressive, highly toxic treatment regimens. Clinical trials for TNBC employing immune checkpoint blockade in combination with chemotherapy show modest prognostic benefit, but the percentage of patients that respond to treatment is low, and patients often succumb to relapsed disease. Here, we show that a combination immunotherapy platform utilizing low dose chemotherapy (FEC) combined with oncolytic virotherapy (oHSV-1) increases tumor-infiltrating lymphocytes, in otherwise immune-bare tumors, allowing 60% of mice to achieve durable tumor regression when treated with immune checkpoint blockade. Whole-tumor RNA sequencing of mice treated with FEC + oHSV-1 shows an upregulation of B cell receptor signaling pathways and depletion of B cells prior to the start of treatment in mice results in complete loss of therapeutic efficacy and expansion of myeloid-derived suppressor cells. Additionally, RNA sequencing data shows that FEC + oHSV-1 suppresses genes associated with myeloid-derived suppressor cells, a key population of cells that drive immune escape and mediate therapeutic resistance. These findings highlight the importance of tumor-infiltrating B cells as drivers of antitumor immunity and their potential role in the regulation of myeloid-derived suppressor cells.

scholarly journals Carbon ion irradiation enhances the antitumor efficacy of dual immune checkpoint blockade therapy both for local and distant sites in murine osteosarcoma

Oncotarget ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 633-646 ◽  
Author(s):  
Yutaka Takahashi ◽  
Tomohiro Yasui ◽  
Kazumasa Minami ◽  
Keisuke Tamari ◽  
Kazuhiko Hayashi ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Ion Irradiation ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Antitumor Efficacy ◽  
Carbon Ion ◽  
Murine Osteosarcoma

scholarly journals Venetoclax Increases Intratumoral Effector T Cells and Antitumor Efficacy in Combination with Immune Checkpoint Blockade

2020 ◽  
Vol 11 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Frederick J. Kohlhapp ◽  
Dipica Haribhai ◽  
Rebecca Mathew ◽  
Ryan Duggan ◽  
Paul A. Ellis ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Effector T Cells ◽  
Checkpoint Blockade ◽  
Antitumor Efficacy

Targeting the tumor microenvironment to overcome immune checkpoint blockade therapy resistance

2020 ◽  
Vol 220 ◽  
pp. 88-96 ◽  
Author(s):  
Yaqi Li ◽  
Jing Liu ◽  
Long Gao ◽  
Yuan Liu ◽  
Fang Meng ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Therapy Resistance ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

scholarly journals Myeloid-Derived Suppressor Cells (MDSCs) in Haematology

2021 ◽  
Vol 11 (1) ◽  
pp. 187
Author(s):  
Nikoleta Bizymi ◽  
Helen A. Papadaki
Keyword(s):  
T Cell ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
T Cell Responses ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunomodulating properties, mainly acting by suppressing T-cell responses [...]

Sign in / Sign up

Export Citation Format

Share Document