Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy

Sarkar, Omar Sadi; Donninger, Howard; Rayyan, Numan Al; Chew, Lewis C.; Stamp, Bryce F.; Zhang, Xiang; Whitt, Aaron G.; Li, Chi; Hall, Melissa Barousse; Mitchell, Robert A.; Zippelius, Alfred; Eaton, John W.; Chesney, Jason; Yaddanapudi, Kavitha

doi:10.1126/sciadv.adg3736

Cited by 24 publications

(14 citation statements)

References 64 publications

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“…MDSCs are derived from bone marrow and play a significant role in the TME. Elevated levels of MDSCs can promote tumor formation and growth as well as inhibit immune responses. , It has been reported that the CSF-1R inhibitor PLX can modulate MDSC subsets in the TME . It was observed that the ratio of CD11b + CD45 + Ly6G int Ly6C low cells was significantly decreased in ascites and tumors of the pIL-12@cR-PssPD, PLX@cR-PssP pIL-12+PLX@PssPD, and pIL-12+PLX@cR-PssPD groups, suggesting a reduction in the infiltration of granulocytic MDSCs.…”

Section: Resultsmentioning

confidence: 99%

Tumor-Microenvironment-Activatable Nanoparticle Mediating Immunogene Therapy and M2 Macrophage-Targeted Inhibitor for Synergistic Cancer Immunotherapy

Hu,

Nie,

Lyu

et al. 2024

ACS Nano

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Immunotherapy has achieved prominent clinical efficacy in combating cancer and has recently become a mainstream treatment strategy. However, achieving broad efficacy with a single modality is challenging, and the heterogeneity of the tumor microenvironment (TME) restricts the accuracy and effectiveness of immunotherapy strategies for tumors. Herein, a TME-responsive targeted nanoparticle to enhance antitumor immunity and reverse immune escape by codelivering interleukin-12 (IL-12) expressing gene and colonystimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (PLX) is presented. The introduction of disulfide bonds and cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) peptides conferred reduction reactivity and tumor targeting to the nanoparticles, respectively. It is hypothesized that activating host immunity by the local expression of IL-12, while modulating the tumor-associated macrophages (TAM) function through blocking CSF-1/CSF-1R signaling, could constitute a feasible approach for cancer immunotherapy. The fabricated functional nanoparticle successfully ameliorated the TME by stimulating the proliferation and activation of T lymphocytes, promoting the repolarization of TAMs, reducing myeloid-derived suppressor cells (MDSCs), and promoting the maturation of dendritic cells (DC) as well as the secretion of antitumor cytokines, which efficiently suppressed tumor growth and metastasis. Finally, substantial changes in the TME were deciphered by single-cell analysis including infiltration of different cells, transcriptional states, secretory signaling and cell−cell communications. These findings provide a promising combinatorial immunotherapy strategy through immunomodulatory nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Tumor-Microenvironment-Activatable Nanoparticle Mediating Immunogene Therapy and M2 Macrophage-Targeted Inhibitor for Synergistic Cancer Immunotherapy

Hu,

Nie,

Lyu

et al. 2024

ACS Nano

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“…BM-MDSCs were cultured as described previously [45] . In short, the tibiae and femora were removed from 12-week-old C57BL/6 J male mice to flush BM cells with PBS, after which clean BM cells were resuspended in RPMI 1640 supplemented with 40 ng/mL murine IL-6 and GM-CSF (Miltenyi Biotec, USA).…”

Section: Methodsmentioning

confidence: 99%

Myeloid-derived suppressor cells promote the formation of abdominal aortic aneurysms through the IL-3-ICOSL-ICOS axis

Lu,

Jin,

Tong

et al. 2023

BBA Advances

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“…M-MDSC induced an increase in adenosine levels, and depletion of adenosine in TME using polyethylene glycolate adenosine deaminase (PEG-ADA) improved the efficacy of immune checkpoint inhibitor (ICI) therapy in mouse studies. This provides new ideas for overcoming resistance to ICI in cancer patients (Sarkar et al 2023 ).…”

Section: Targeting Mdsc-related Therapeutic Strategiesmentioning

confidence: 99%

Role played by MDSC in colitis-associated colorectal cancer and potential therapeutic strategies

Wang,

Yin

2024

J Cancer Res Clin Oncol

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Colitis-associated colorectal cancer has been a hot topic in public health issues worldwide. Numerous studies have demonstrated the significance of myeloid-derived suppressor cells (MDSCs) in the progression of this ailment, but the specific mechanism of their role in the transformation of inflammation to cancer is unclear, and potential therapies targeting MDSC are also unclear. This paper outlines the possible involvement of MDSC to the development of colitis-associated colorectal cancer. It also explores the immune and other relevant roles played by MDSC, and collates relevant targeted therapies against MDSC. In addition, current targeted therapies for colorectal cancer are analyzed and summarized.

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Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy

Cited by 24 publications

References 64 publications

Tumor-Microenvironment-Activatable Nanoparticle Mediating Immunogene Therapy and M2 Macrophage-Targeted Inhibitor for Synergistic Cancer Immunotherapy

Tumor-Microenvironment-Activatable Nanoparticle Mediating Immunogene Therapy and M2 Macrophage-Targeted Inhibitor for Synergistic Cancer Immunotherapy

Myeloid-derived suppressor cells promote the formation of abdominal aortic aneurysms through the IL-3-ICOSL-ICOS axis

Role played by MDSC in colitis-associated colorectal cancer and potential therapeutic strategies

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