scholarly journals The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors

2022 ◽  
Vol 12 ◽  
Author(s):  
Huan Tong ◽  
He Wei ◽  
Alhaji Osman Smith ◽  
Juan Huang
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Epigenetic Modification ◽  
Advanced Malignancy ◽  
Tumor Drug Resistance ◽  
New Strategies

Tumor immunotherapy, one of the efficient therapies in cancers, has been called to the scientific community’s increasing attention lately. Among them, immune checkpoint inhibitors, providing entirely new modalities to treat cancer by leveraging the patient’s immune system. They are first-line treatments for varieties of advanced malignancy, such as melanoma, gastrointestinal tumor, esophageal cancer. Although immune checkpoint inhibitors (ICIs) treatment has been successful in different cancers, drug resistance and relapses are common, such as in colorectal cancer. Therefore, it is necessary to improve the efficacy of immune checkpoint therapy for cancer patients who do not respond or lowly response to current treatments. N6-methyladenosine (m6A), as a critical regulator of transcript expression, is the most frequently internal modification of mRNA in the human body. Recently, it has been proposed that m6A epigenetic modification is a potential driver of tumor drug resistance. In this report, we will briefly outline the relevant mechanisms, general treatment status of immune checkpoint inhibitors in colorectal cancer, how m6A epigenetic modifications regulate the response of ICIs in CRC and provide new strategies for overcoming the resistance of ICIs in CRC.

scholarly journals LMD-10. The role of immune checkpoint inhibitors in leptomeningeal disease: a systematic review

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii9-iii9
Author(s):  
Paolo Palmisciano ◽  
Ali S Haider ◽  
Chibueze D Nwagwu ◽  
Waseem Wahood ◽  
Navraj S Sagoo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Leptomeningeal Disease ◽  
Mri Findings ◽  
Primary Tumors ◽  
Advanced Malignancy

Abstract Background Leptomeningeal disease (LMD) is a devastating complication of advanced malignancy with a poor prognosis and limited therapeutic options. Whether immune checkpoint inhibitors (ICIs) alter disease course is unknown. Methods We searched PubMed, EMBASE, Scopus, Cochrane, and clinicaltrials.gov according to PRISMA guidelines to analyze the therapeutic role and toxicity profiles of ICIs in the management of LMD. Studies reporting clinical outcome data of patients with LMD treated with ICIs were included. A comprehensive review of clinical characteristics and survival analysis was conducted. Results We included 14 studies encompassing 61 patients. The median age at LMD diagnosis was 57 years (female=63.9%). Lung cancer (44.3%), breast cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Parenchymal brain metastases occurred in 37 patients, mostly treated with radiotherapy (83.3%). LMD most frequently presented with headache (42.1%) and was diagnosed by MRI findings (leptomeningeal T1-contrast enhancement: 96.7%) and/or positive cerebrospinal fluid cytology (86.5%). Patients received ICIs for a median duration of 7 months (range, 0.5–58.0): pembrolizumab (49.2%), nivolumab (32.8%), and/or ipilimumab (18.0%). The most common concurrent LMD treatments were radiotherapy (54.7%) and steroids (35.7%). Radiological responses at 6-months were complete (33.3%) and partial response (12.5%), stable disease (33.3%), and progression (20.8%). 22 patients developed ICI-related adverse events, mostly mild (100%) and uncommonly severe (15.6%). Median progression-free survival was 5.1 months, median overall survival was 6.3 months, and 12-month survival was 32.1%. Survival was correlated with ICIs (P=0.042), but not with primary tumors (P=0.144). Patients concurrently receiving steroids showed worse survival (P=0.040), with a median overall survival of 1.9 months. Conclusion ICI therapy shows promise and appears to be well-tolerated in patients with LMD. Concurrent use of steroids is associated with worse survival. The role of ICIs in the multimodal management of LMD and their combination with steroids requires further analysis.

scholarly journals Neutrophils Extracellular Traps Inhibition Improves PD-1 Blockade Immunotherapy in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5333
Author(s):  
Hongji Zhang ◽  
Yu Wang ◽  
Amblessed Onuma ◽  
Jiayi He ◽  
Han Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Dnase I ◽  
Neutrophil Extracellular Trap ◽  
Advanced Malignancy ◽  
Extracellular Traps

Immune checkpoint inhibitors can improve the prognosis of patients with advanced malignancy; however, only a small subset of advanced colorectal cancer patients in microsatellite-instability-high or mismatch-repair-deficient colorectal cancer can benefit from immunotherapy. Unfortunately, the mechanism behind this ineffectiveness is unclear. The tumor microenvironment plays a critical role in cancer immunity, and may contribute to the inhibition of immune checkpoint inhibitors and other novel immunotherapies in patients with advanced cancer. Herein, we demonstrate that the DNase I enzyme plays a pivotal role in the degradation of NETs, significantly dampening the resistance to anti-PD-1 blockade in a mouse colorectal cancer model by attenuating tumor growth. Remarkably, DNase I decreases tumor-associated neutrophils and the formation of MC38 tumor cell-induced neutrophil extracellular trap formation in vivo. Mechanistically, the inhibition of neutrophil extracellular traps with DNase I results in the reversal of anti-PD-1 blockade resistance through increasing CD8+ T cell infiltration and cytotoxicity. These findings signify a novel approach to targeting the tumor microenvironment using DNase I alone or in combination with immune checkpoint inhibitors.

scholarly journals Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Miaoqin Chen ◽  
Shiman Hu ◽  
Yiling Li ◽  
Ting Ting Jiang ◽  
Hongchuan Jin ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Tumor Control ◽  
New Strategies

AbstractCancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment. However, there are many patients who failed to benefit from these therapies, highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors. In this review, we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy. Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function, it seems that harnessing the nuclear acid-mediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.

scholarly journals The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Nora Chokr ◽  
Rima Patel ◽  
Kapil Wattamwar ◽  
Samer Chokr
Keyword(s):  
Myelodysplastic Syndromes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Epigenetic Modification ◽  
Wide Spectrum ◽  
Treatment Options ◽  
Treatment Method ◽  
Hematologic Malignancies

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous investigations on the role of immunomodulatory drugs as potential treatment options. Epigenetic modification via immune check point inhibition, while well established as a treatment method for advanced solid tumors, is a new approach being considered in hematologic malignancies including high risk MDS. Several trials are looking at the efficacy of these agents in MDS, as frontline therapy and in relapse, both as monotherapy and in combination with other drugs. In this review, we explore the utility of immune checkpoint inhibitors in MDS and current research evaluating their efficacy.

scholarly journals P09.25 Role of Immune Checkpoint Inhibitors (ICPi) in KRAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

2021 ◽  
Vol 16 (3) ◽  
pp. S300-S301
Author(s):  
M. Peravali ◽  
C. Gomes-Lima ◽  
E. Tefera ◽  
M. Baker ◽  
M. Sherchan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

Sign in / Sign up

Export Citation Format

Share Document