scholarly journals Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape

Cell ◽  
2021 ◽  
Author(s):  
Mary Bushman ◽  
Rebecca Kahn ◽  
Bradford P. Taylor ◽  
Marc Lipsitch ◽  
William P. Hanage
Keyword(s):  
Immune Escape ◽  
Population Impact

scholarly journals Population Impact of SARS-CoV-2 Variants with Enhanced Transmissibility and/or Partial Immune Escape

2021 ◽  
Author(s):  
Mary Bushman ◽  
Rebecca Kahn ◽  
Bradford P. Taylor ◽  
Marc Lipsitch ◽  
William P. Hanage
Keyword(s):  
Immune Escape ◽  
Population Impact

scholarly journals Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape

2021 ◽  
Author(s):  
Mary Bushman ◽  
Rebecca Kahn ◽  
Bradford P. Taylor ◽  
Marc Lipsitch ◽  
William P. Hanage
Keyword(s):  
Mathematical Model ◽  
High Frequency ◽  
Immune Escape ◽  
Low Risk ◽  
Population Impact ◽  
Nonpharmaceutical Interventions ◽  
Induced Immunity ◽  
Do So

SummarySARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from infection- and vaccine-induced immunity. Much effort has been devoted to measuring these phenotypes, but predicting their impact on the course of the pandemic – especially that of immune escape – remains a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility easily rise to high frequency, whereas partial immune escape, on its own, often fails to do so. However, when these phenotypes are combined, enhanced transmissibility can carry the variant to high frequency, at which point partial immune escape may limit the ability of vaccination to control the epidemic. Our findings suggest that moderate immune escape poses a low risk unless combined with a substantial increase in transmissibility.

Polarization of M2 Macrophages to Promote Tumor Immune Escape via Il-10 in SCLC but Not NSCLC Patients

2019 ◽  
Author(s):  
Xintong Hu ◽  
Yue Gu ◽  
Songchen Zhao ◽  
Shucheng Hua ◽  
Yanfang Jiang
Keyword(s):  
Immune Escape ◽  
M2 Macrophages ◽  
Tumor Immune Escape ◽  
Nsclc Patients

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Escape ◽  
Hypoxia Inducible Factor ◽  
Hpv Infection ◽  
Advanced Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

Progress on the Mechanism for Aspirin’s Anti-tumor Effects

2020 ◽  
Vol 22 (1) ◽  
pp. 105-111
Author(s):  
Lin Zheng ◽  
Weibiao Lv ◽  
Yuanqing Zhou ◽  
Xu Lin ◽  
Jie Yao
Keyword(s):  
Platelet Aggregation ◽  
Energy Metabolism ◽  
Side Effects ◽  
Energy Production ◽  
Immune Escape ◽  
Inflammatory Responses ◽  
Mechanisms Of Action ◽  
Proliferation And Metastasis ◽  
Review Current ◽  
Granule Release

: Since its discovery more than 100 years ago, aspirin has been widely used for its antipyretic, analgesic, anti-inflammatory, and anti-rheumatic activities. In addition to these applications, it is increasingly becoming clear that the drug also has great potential in the field of cancer. Here, we briefly review current insights of aspirin’s anti-tumor effects. These are multiple and vary from inhibiting the major cellular mTOR pathways, acting as a calorie-restricted mimetic by inhibition of energy production, suppressing platelet aggregation and granule release, inhibiting immune escape of tumor cells, to decreasing inflammatory responses. We consider these five mechanisms of action the most significant of aspirin’s anti-tumor effects, whereby the anti-tumor effect may ultimately stem from its inhibition of energy metabolism, platelet function, and inflammatory response. As such, aspirin can play an important role to reduce the occurrence, proliferation, and metastasis of various types of tumors. However, most of the collected data are still based on epidemiological investi-gations. More direct and effective evidence is needed, and the side effects of aspirin intake need to be solved before this drug can be widely applied in cancer treatment.

scholarly journals PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002844
Author(s):  
Alexander Stein ◽  
Donjete Simnica ◽  
Christoph Schultheiß ◽  
Rebekka Scholz ◽  
Joseph Tintelnot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Metastatic Colorectal Cancer ◽  
Multispectral Imaging ◽  
Standard Treatment ◽  
Immune Escape ◽  
Killer Cell ◽  
Cell Killing ◽  
Antitumor Effects ◽  
High Affinity

BackgroundIn patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration.MethodsWe treated 43 patients with predominantly microsatellite stable RAS/BRAF wild-type mCRC on a phase II trial combining chemotherapy with the epidermal growth factor receptor antibody cetuximab and the programmed cell death ligand 1 (PD-L1) antibody avelumab. We performed next-generation gene panel sequencing for mutational typing of tumors and liquid biopsy monitoring as well as digital droplet PCR to confirm individual mutations. Translational analyses included tissue immunohistochemistry, multispectral imaging and repertoire sequencing of tumor-infiltrating T cells. Detected PD-L1 mutations were mechanistically validated in CRISPR/Cas9-generated cell models using qRT-PCR, immunoblotting, flow cytometry, complement-dependent cytotoxicity assay, antibody-dependent cytotoxicity by natural killer cell degranulation assay and LDH release assay as well as live cell imaging of T cell mediated tumor cell killing.ResultsCirculating tumor DNA showed rapid clearance in the majority of patients mirroring a high rate of early tumor shrinkage. In 3 of 13 patients expressing the high-affinity Fcγ receptor 3a (FcγR3a), tumor subclones with PD-L1 mutations were selected that led to loss of tumor PD-L1 by nonsense-mediated RNA decay in PD-L1 K162fs and protein degradation in PD-L1 L88S. As a consequence, avelumab binding and antibody-dependent cytotoxicity were impaired, while T cell killing of these variant clones was increased. Interestingly, PD-L1 mutant subclones showed slow selection dynamics reversing on avelumab withdrawal and patients with such subclones had above-average treatment benefit. This suggested that the PD-L1 mutations mediated resistance to direct antitumor effects of avelumab, while at the same time loss of PD-L1 reduced biological fitness by enhanced T cell killing limiting subclonal expansion.ConclusionThe addition of avelumab to standard treatment appeared feasible and safe. PD-L1 mutations mediate subclonal immune escape to avelumab in some patients with mCRC expressing high-affinity FcγR3a, which may be a subset experiencing most selective pressure. Future trials evaluating the addition of avelumab to standard treatment in MSS mCRC are warranted especially in this patient subpopulation.Trial registration numberNCT03174405.

Sign in / Sign up

Export Citation Format

Share Document