Novel genomic signature predictive of response to immune checkpoint blockade: A pan-cancer analysis from project Genomics Evidence Neoplasia Information Exchange (GENIE)

2021 ◽  
Author(s):  
Nishwant Swami ◽  
William L. Hwang ◽  
Jimmy A. Guo ◽  
Hannah Hoffman ◽  
Matthew C. Abramowitz ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Information Exchange ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Genomic Signature ◽  
Pan Cancer

scholarly journals A pan-cancer immunogenomic atlas for immune checkpoint blockade immunotherapy

2021 ◽  
pp. canres.2335.2021
Author(s):  
Jing Yang ◽  
Shilin Zhao ◽  
Jing Wang ◽  
Quanhu Sheng ◽  
Qi Liu ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Pan Cancer

scholarly journals Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chi Yan ◽  
Ann Richmond
Keyword(s):  
Immune Checkpoint ◽  
Tumor Response ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Type I ◽  
List Type ◽  
Cancer Types ◽  
Pan Cancer ◽  
Cancer Bioinformatics

Highlights CD40 expression correlates with the type I anti-tumor response and better survival. Pan-cancer bioinformatics characterization reveals reduced CD40 expression in 11 cancer types, including RASmut melanoma compared to nevi. RAS mutation correlates with reduced CD40 expression in malignant melanoma. CD40 expression is associated with better response to immune checkpoint blockade therapy in melanoma.

scholarly journals Plasma-based microsatellite instability detection strategy to guide immune checkpoint blockade treatment

2020 ◽  
Vol 8 (2) ◽  
pp. e001297
Author(s):  
Zhenghang Wang ◽  
Xiaochen Zhao ◽  
Chan Gao ◽  
Jifang Gong ◽  
Xicheng Wang ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Gastrointestinal Cancer ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Blood Draw ◽  
Detection Strategy ◽  
Tumor Mutational Burden ◽  
Pan Cancer

BackgroundMicrosatellite instability (MSI) represents the first pan-cancer biomarker approved to guide immune checkpoint blockade (ICB) treatment. However its widespread testing, especially outside of gastrointestinal cancer, is hampered by tissue availability.MethodsAn algorithm for detecting MSI from peripheral blood was established and validated using clinical plasma samples. Its value for predicting ICB efficacy was evaluated among 60 patients with advanced gastrointestinal cancer. The landscape of MSI in blood was also explored among 5138 advanced solid tumors.ResultsThe algorithm included 100 microsatellite markers with high capture efficiency, sensitivity, and specificity. In comparison with orthogonal tissue PCR results, the method displayed a sensitivity of 82.5% (33/40) and a specificity of 96.2% (201/209), for an overall accuracy of 94.0% (234/249). When the clinical validation cohort was dichotomized by pretreatment blood MSI (bMSI), bMSI-high (bMSI-H) predicted both improved progression-free survival and overall survival than the blood microsatellite stable (bMSS) patients (HRs: 0.431 and 0.489, p=0.005 and 0.034, respectively). Four patients with bMSS were identified to have high blood tumor mutational burden (bTMB-H) and trended towards a better survival than the bMSS-bTMB-low (bTMB-L) subset (HR 0.026, 95% CI 0 to 2.635, p=0.011). These four patients with bMSS-bTMB-H plus the bMSI-H group collectively displayed significantly improved survival over the bMSS-bTMB-L patients (HR 0.317, 95% CI 0.157 to 0.640, p<0.001). Pan-cancer prevalence of bMSI-H was largely consistent with that shown for tissue except for much lower rates in endometrial and gastrointestinal cancers, and a remarkably higher prevalence in prostate cancer relative to other cancer types.ConclusionsWe have developed a reliable and robust next generation sequencing-based bMSI detection strategy which, in combination with a panel enabling concurrent profiling of bTMB from a single blood draw, may better inform ICB treatment.

Analysis of Advanced Melanomas Changed from Immune Checkpoint Blockade Therapy to Palliative Care

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

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

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.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

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.

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