Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab

Tobin, Richard P.; Jordan, Kimberly R.; Robinson, William A.; Davis, Dana M.; Borges, Virginia F.; González, René; Lewis, Karl D.; McCarter, Martin D.

doi:10.1016/j.intimp.2018.08.007

Cited by 140 publications

(104 citation statements)

References 43 publications

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“…However, drugs for inducing MDSCs to mature received more researches, e.g. oxaliplatin (Kim and Kim, 2019), all-trans retinoic acid (Tobin et al, 2018), resveratrol (Zhao et al, 2018a).…”

mentioning

confidence: 99%

Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

et al. 2020

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be villainy after treatment, when these drugs suppress the immunosuppressive ability of CD11b + Gr-1 + cells and promote it mature to replenish dendritic cell, at the same time. Generally, JHD may be a complementary and alternative drug for attenuating the immunosuppressive status induced by hepatocellular carcinoma, possibly by promoting differentiation and inhibiting the immunosuppressive activity of MDSCs.

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“…However, drugs for inducing MDSCs to mature received more researches, e.g. oxaliplatin (Kim and Kim, 2019), all-trans retinoic acid (Tobin et al, 2018), resveratrol (Zhao et al, 2018a).…”

mentioning

confidence: 99%

Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

et al. 2020

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“…There exist different approaches to target MDSCs: inhibition of MDSC accumulation, blocking of MDSC recruitment, and inhibition of MDSC function [32] (Table 1). Recently, MDSC inhibition in combination with immunotherapy have shown promising results in humans [43]. Clinical trials targeting MDSCs are summarized in Table 2.…”

Section: Mdsc Targeting For Cancer Treatmentsmentioning

confidence: 99%

“…The antitumor effects of ATRA have been extensively studied in numerous studies in the past decades, but MDSCs were not almost evaluated in these studies [47]. In some clinical studies, ATRA has been reported to reduce the frequencies of circulating MDSCs [43,48,49]. ATRA treatment improved the immune response to cancer vaccine [48] and antigen-specific T-cell response [49].…”

Section: Inhibition Of Mdsc Accumulationmentioning

confidence: 99%

The emerging role of myeloid-derived suppressor cells in radiotherapy

et al. 2020

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Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

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“…Combination of all-trans retinoic acid (ATRA) with ipilimumab was reported to decrease frequency of circulating MDSC as well as the expression of PD-L1, IL-10, and indoleamine 2,3-dioxygenase by MDSC, whereas in the ipilimumab monotherapy group the MDSC frequency increased during the treatment [125]. Furthermore, patients receiving combinational treatment tend to have an increased activated CD107a + IFN-γ + CD8 + T cell numbers compared to the patients treated with ipilimumab alone.…”

Section: Increasing Effectiveness Of Ici Therapymentioning

confidence: 99%

“…TIGIT + Tregs showed higher immunosuppressive potential than their TIGITcounterparts [147]. In malignant melanoma, the co-expression of PD-L1, LAG-3, TIM-3 and TIGIT was demonstrated to induce CD8 + TILs with most exhausted phenotype [125,126]. Double blockage of PD-1 and TIGIT in melanoma led to an increased proliferation and cytokine production of CD8 + TIL and was considered to be a promising approach in immunotherapy [148].…”

Section: Other Ici In Malignant Melanomamentioning

confidence: 99%

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

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Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

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Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab

Abstract: These results illustrate the importance of MDSCs in immunotherapy resistance and provide evidence that targeting MDSCs in cancer patients may augment immunotherapeutic approaches.

Cited by 140 publications

References 43 publications

Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

The emerging role of myeloid-derived suppressor cells in radiotherapy

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

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