Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

Chen, Xi; Pan, Xiaohui; Zhang, Wenxin; Guo, Hongjie; Cheng, Shu‐Yuan; He, Qiaojun; Yang, Bo; Ding, Ling

doi:10.1016/j.apsb.2019.09.006

Cited by 125 publications

(92 citation statements)

References 107 publications

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“…ICI can also be combined with DC vaccines, which can augment the generation of tumor antigen-specific effector CD8+ T cells, resulting in more effective anti-tumor T cell immunity and improved disease outcome. ICI therapy may also be used in combination with anti-angiogenic inhibitors (such as anti-VEGF antibodies) [127], poly (ADP ribose) polymerase (PARP) inhibitors [128], or epigenetic modifiers (such as decitabine) [129,130], all of which can result in heightened CD8+ T cell anti-tumor responses through a variety of mechanisms.…”

Section: Immune Checkpoint Inhibition Therapy In Ovarian Cancermentioning

confidence: 99%

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

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This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.

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Section: Immune Checkpoint Inhibition Therapy In Ovarian Cancermentioning

confidence: 99%

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

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“…An effective response to anti-PD-L1/anti-PD-1 therapy requires the establishment of a complete immune cycle. The damage of immune circulation is an important cause of the failure of immunotherapy, which can be recovered by epigenetic modification [ 82 ]. Related studies have investigated the role of DNA methylation in inhibiting molecular transcription in regulatory myelinated inhibitory cells (identified as CD33HLA-DR), and compared with APC.…”

Section: Epigenetic Modification Of Mdscsmentioning

confidence: 99%

Connections between Metabolism and Epigenetic Modification in MDSCs

Dai

Wang

et al. 2020

IJMS

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Myeloid-derived suppressor cells (MDSCs) are major immunosuppressive cells in the tumor microenvironment (TME). During the differentiation and development of MDSCs from myeloid progenitor cells, their functions are also affected by a series of regulatory factors in the TME, such as metabolic reprogramming, epigenetic modification, and cell signaling pathways. Additionally, there is a crosstalk between these regulatory factors. This review mainly introduces the metabolism (especially glucose metabolism) and significant epigenetic modification of MDSCs in the TME, and briefly introduces the connections between metabolism and epigenetic modification in MDSCs, in order to determine the further impact on the immunosuppressive effect of MDSCs, so as to serve as a more effective target for tumor therapy.

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“…Furthermore, there is increasing evidence that epigenetic agents can promote the anti-cancer immune response via multiple mechanisms including increased antigen release and antigen presentation [steps 1 and 2 of the Cancer Immunity Cycle (Fig. 2)], T cell trafficking and infiltration into the tumor (steps 4 and 5) as well as restoring effector T cell function (step 7), suggesting potential synergy with checkpoint inhibitors particularly in immunologically 'cold' tumors [98].…”

Section: Combination Checkpoint Blockade and Epigenetic Modifiersmentioning

confidence: 99%

Targeting the immune milieu in gastrointestinal cancers

2020

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Gastrointestinal (GI) cancers are among the most common and lethal solid tumors worldwide. Unlike in malignancies such as lung, renal and skin cancers, the activity of immunotherapeutic agents in GI cancers has, on the whole, been much less remarkable and do not apply to the majority. Furthermore, while incremental progress has been made and approvals for use of immune checkpoint inhibitors (ICIs) in specific subsets of patients with GI cancers are coming through, in a population of ‘all-comers’, it is frequently unclear as to who may benefit most due to the relative lack of reliable predictive biomarkers. For most patients with newly diagnosed advanced or metastatic GI cancer, the mainstay of treatment still involves chemotherapy and/or a targeted agent however, beyond the second-line this paradigm confers minimal patient benefit. Thus, current research efforts are concentrating on broadening the applicability of ICIs in GI cancers by combining them with agents designed to beneficially remodel the tumor microenvironment (TME) for more effective anti-cancer immunity with intention of improving patient outcomes. This review will discuss the currently approved ICIs available for the treatment of GI cancers, the strategies underway focusing on combining ICIs with agents that target the TME and touch on recent progress toward identification of predictors of sensitivity to immune checkpoint blockade in GI cancers.

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Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

Cited by 125 publications

References 107 publications

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Connections between Metabolism and Epigenetic Modification in MDSCs

Targeting the immune milieu in gastrointestinal cancers

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