Research trends and public interests of immune checkpoint blockade in melanoma: a visualization and bibliometric analysis (Preprint)

2021 ◽  
Author(s):  
Yantao Xu ◽  
Zixi Jiang ◽  
Xinwei Kuang ◽  
Xiang Chen ◽  
Hong Liu

BACKGROUND Melanoma is one of the most life-threatening skin cancers and immune checkpoint blockers (ICB) are widely used in the treatment of melanoma because of their remarkable efficacy. OBJECTIVE This study aimed to conduct a comprehensive bibliometric analysis of ICB in melanoma for the past decades, while exploring the research trends and public interests of immune checkpoint blockade in melanoma. METHODS We summarized the articles embodied in web of science core collection about immune checkpoint blockers in melanoma each year from 1950 to 2020. R package Bibliometrix was used to data extraction and the visualization of the distribution of publication years and top 10 core authors. The keywords citation burst analysis and co-citation network are performed by CiteSpace. Gunn map online world map was used to evaluate the distribution of countries and regions. Ranking was performed using the Standard Competition Ranking method. Except for these, the results of co-authorship analysis, co-occurrence are analyzed and visualized by VOSviewer. RESULTS After removing duplication, totally 9169 documents were included. Distribution of annual publications shows that the number of publications rose sharply from 2015 onwards, to a peak in 2020 or is yet to come. Spatial distribution indicated that there is a large gap between the amount of document published in other countries and the United States. The co-authorship analysis results clustered all 149 top published institution into 8 clusters, each approximately indicated one country, suggested that the international cooperation among various institutions should be strengthened, while the core author extraction indicate the publication peak change of authors. Keyword analysis unraveled the keywords clustering and top citation burst. Co-citation analysis of references analysis the reference from 2010 to 2020, unravel the citation number and centrality of top article. CONCLUSIONS This study revealed the trends in research interest and public interest of immune checkpoint blockade in melanoma, which may pave the way for further research.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS454-TPS454
Author(s):  
Ilenia Pellicciotta ◽  
Emily Linda Alouani ◽  
Alexander Raufi ◽  
Samuel M Pan ◽  
Jianhua Hu ◽  
...  

TPS454 Background: Pancreas adenocarcinoma (PDAC) is an aggressive cancer projected to be the second leading cause of cancer-related death in the United States by 2030 for which improved treatment options are desperately needed. Immune checkpoint blockade (ICB) for PDAC has failed as monotherapy in early phase clinical trials likely due to a highly immunosuppressive tumor microenvironment. The CXCR4/CXCL12 axis is a key immune evasion mechanism thought to deter CD8+ T-cells (CTLs) from infiltrating the tumor. We performed a large seven arm survival and biopsy/necropsy study in KPC mice (KrasLSL.G12D/+;p53R172H/+;Pdx1Cretg/+) where we demonstrate that addition of gemcitabine to CXCR4 inhibition in combination with ICB, enhanced tumor stabilization and neoplastic cell death, and improved survival by 50 percent. Multiplex immunofluorescence indicated an increased CTL to regulatory T-cell ratio and clustering of CTLs around neoplastic cells. Presented here is a trial-in progress that will evaluate combination of a CXCR4 inhibitor, ICB, and chemotherapy in treatment naïve patients with PDAC. Methods: This is a multicenter, single arm, open-label phase 2 study of combination motixafortide 1.25mg/kg SC monotherapy for 5 days during priming followed by twice weekly, cemiplimab 350mg IV once every 21 days, gemcitabine 1000mg/m2 IV with nab-paclitaxel 125mg/m2 IV on days 1, 8, and 15 every 28 days. Patients with histologically confirmed metastatic PDAC who have not received prior therapy will be enrolled. The primary endpoint is overall response rate by 16 weeks. A response rate greater than 45% by 16 weeks is considered promising, whereas a response rate of less than 23% is considered not promising. We will use a Simon optimal 2-stage design, where we will enroll 10 patients in the first stage. If 3 or more patients meet the endpoint in the first stage, the study will be expanded to a total of 40 patients. If a total of 14 or more patients achieve CR or PR by 16 weeks, the agent will be considered promising and worthy of further study. Secondary endpoints include safety, mPFS, disease control rate (DCR), and mOS. Correlative aims include analyses of pre- and on-treatment biopsies with quantitative multiplex immunofluorescence, RNA-sequencing, and generation of patient derived organoids for association with clinical benefit and to determine mechanisms of action/resistance. An interim analysis will be performed at the conclusion of the stage I portion of the study. Clinical trial information: NCT04543071.


Author(s):  
Emi Noguchi ◽  
Tadahiko Shien ◽  
Hiroji Iwata

Abstract Over the past 10 years, immunotherapy with immune checkpoint inhibitors has revolutionized the management of various cancers. However, immunotherapy in breast cancer has not been successful. Breast cancer has long been recognized as an immunologically ‘cold’ tumor, although a higher frequency of tumor-infiltrating lymphocytes present in certain subtypes and an association between tumor-infiltrating lymphocytes and favorable prognosis have been reported. In March 2019, the combination of atezolizumab and nanoparticle albumin-bound paclitaxel was granted accelerated approval in the United States for the treatment of programmed death-ligand 1-positive advanced or metastatic triple-negative breast cancer. This finally opened the door for immune checkpoint blockade therapy for breast cancer. Several clinical trials have been conducted using different combinations of immune checkpoint inhibitors and chemotherapy or targeted agents in various treatment settings for metastatic breast cancer and early-stage breast cancer. In this review, we summarize recent advances in immune checkpoint blockade therapy and predictive biomarkers in breast cancer.


2018 ◽  
Vol 80 (1) ◽  
pp. 51-55
Author(s):  
Ai KAJITA ◽  
Osamu YAMASAKI ◽  
Tatsuya KAJI ◽  
Hiroshi UMEMURA ◽  
Keiji IWATSUKI

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.


2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.


Sign in / Sign up

Export Citation Format

Share Document