The clinical evidence for targeting human myeloid-derived suppressor cells in cancer patients

Tobin, Richard P.; Davis, Dana M.; Jordan, Kimberly R.; McCarter, Martin D.

doi:10.1189/jlb.5vmr1016-449r

Cited by 50 publications

(47 citation statements)

References 89 publications

(120 reference statements)

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“…136 Mesenchymal stromal cells (MSC) are nonhematopoietic progenitor cells with immunomodulatory and antibacterial properties, [137][138] that improve immune responses and lung pathology in human and murine TB. [139][140] Another immunotherapeutic approach involves modulation of immune regulatory cells, specifically myeloid-derived suppressor cells (MDSC) [141][142] MDSC are increased in TB, display T-cell immunosuppressive properties, [143][144][145] and harbour Mtb, suggesting that MDSC-targeting strategies should also be considered in TB HDT design. The promise of use T-cell therapy, with or without T-cell receptor (TCR) manipulations to increase affinity for antigen has shown promise for CMV treatment, and could be beneficial in TB.…”

Section: Cellular Therapymentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

287

261

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Cellular Therapymentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

287

261

View full text Add to dashboard Cite

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“…Interestingly, these "non-inflamed" tumors have been reported to be less responsive to checkpoint inhibitors, and the ability to inhibit pro-tumorigenic myeloid cells will be an important clinical strategy going forward in immune-oncology (52 …”

Section: Caspase-1 Expression In the Tme Correlates With Worse Prognosismentioning

confidence: 99%

Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation

Zeng

Korrer

et al. 2018

Cancer Immunology Research

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“…Therefore, MDSCs are an attractive target for optimizing anticancer treatment. Indeed, cancer studies using animal models have documented benefits from depleting MDSCs or blocking their function (7,8).…”

Section: Introductionmentioning

confidence: 99%

Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the In Vitro Integrity of T Cells from Cancer Patients

Kobayashi

Chung

Beg

et al. 2019

Clinical Cancer Research

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Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment. Patients with metastatic cancer ( = 198) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14HLA-DR MDSCs. Their suppressor function was assessed by coculture with autologous T cells, and the ability of anti-DC-HIL or anti-PDL1 mAb to reverse such function was determined. Tumor expression of these receptors was examined histologically, and the antitumor activity of the mAb was evaluated by attenuated growth of colon cancers in mice. Patients with metastatic cancer had high blood levels of DC-HIL MDSCs compared with healthy controls. Anti-DC-HIL mAb reversed the function in ∼80% of cancer patients tested, particularly for colon cancer. Despite very low expression on blood MDSCs, anti-PDL1 mAb was as effective as anti-DC-HIL mAb in reversing MDSC function, a paradoxical phenomenon we found to be due to upregulated expression of PDL1 by T-cell-derived IFNγ in cocultures. DC-HIL is not expressed by colorectal cancer cells but by CD14 cells infiltrating the tumor. Finally, anti-DC-HIL mAb attenuated growth of preestablished colon tumors by reducing MDSCs and increasing IFNγ-secreting T cells in the tumor microenvironment, with similar outcomes to anti-PDL1 mAb. Blocking DC-HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC-HIL MDSCs.

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The clinical evidence for targeting human myeloid-derived suppressor cells in cancer patients

Cited by 50 publications

References 89 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell–Independent Tumor Proliferation

Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the In Vitro Integrity of T Cells from Cancer Patients

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