Immune‐related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies DOI
M. Lisa Zhang, Azfar Neyaz, Deepa T. Patil

et al.

Histopathology, Journal Year: 2019, Volume and Issue: 76(2), P. 233 - 243

Published: July 30, 2019

Aims Immune checkpoint inhibitors (ICIs) improve survival across a range of malignancies but are also associated with spectrum gastrointestinal (GI) immune‐related adverse events (GI‐irAEs). The aims this study were to explore the diagnostic value gastric and duodenal biopsies address considerations in differential diagnosis. Methods results We identified 39 patients who treated ICIs had subsequent upper GI biopsy. recorded clinical data endoscopic findings, reviewed their gastric, colonic biopsies. Twenty‐one (54%) an anti‐programmed cell death protein 1 (PD‐1)/anti‐programmed ligand antibody alone, 17 (44%) combination anti‐cytotoxic T‐lymphocyte‐associated protein‐4 anti‐PD‐1 antibodies. Thirty‐two (82%) presented diarrhoea. Gastric alterations included periglandular inflammation granulomas, changes villous blunting, intraepithelial lymphocytosis, neutrophilic activity. recognised four patterns injury: (i) acute self‐limiting colitis; (ii) lymphocytic (iii) collagenous (iv) apoptosis‐only. Twenty‐nine (74%) 10 (26%) diagnosed clinically as positive negative for GI‐irAEs, respectively. ( P = 0.004) increased number lamina propria mononuclear cells 0.04) correlated diagnosis GI‐irAE. Histological ICI injury more often (71%) than (65%). Conclusions morphological ICI‐related disease is broad, mimics infectious inflammatory diseases. represents one characteristic histological features GI‐irAEs. underscores importance comprehensive review lower

Language: Английский

Hallmarks of response, resistance, and toxicity to immune checkpoint blockade DOI Creative Commons
Golnaz Morad, Beth A. Helmink, Padmanee Sharma

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(21), P. 5309 - 5337

Published: Oct. 1, 2021

Language: Английский

Citations

1094
Immune-related adverse events of checkpoint inhibitors DOI
Manuel Ramos‐Casals, Julie R. Brahmer, Margaret K. Callahan

et al.

Nature Reviews Disease Primers, Journal Year: 2020, Volume and Issue: 6(1)

Published: May 7, 2020

Language: Английский

Citations

1027
Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy DOI Creative Commons

Mengze Lv,

Meixia Chen,

Rui Zhang

et al.

Cell Research, Journal Year: 2020, Volume and Issue: 30(11), P. 966 - 979

Published: Aug. 24, 2020

Abstract CD8 + T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1, an acts brakes to prevent cell overreaction under normal conditions but exploited tumor cells escape immune surveillance. Immune checkpoint inhibitors have revolutionized therapeutics removing such brakes. Unfortunately, only a minority of patients respond immunotherapies presumably due inadequate immunity. Antitumor immunity depends on activation cGAS-STING pathway, as STING-deficient mice fail stimulate tumor-infiltrating dendritic (DCs) activate cells. STING agonists also enhance natural killer (NK) mediate cell-resistant tumors. Therefore been intensively sought after. We previously discovered that manganese (Mn) indispensable for host defense against cytosolic dsDNA activating cGAS-STING. Here we report Mn essential in innate sensing tumors enhances adaptive responses Mn-insufficient had significantly enhanced growth metastasis, with greatly reduced Mechanically, 2+ promoted DC macrophage maturation tumor-specific antigen presentation, augmented differentiation, NK activation, increased memory Combining inhibition synergistically boosted antitumor efficacies anti-PD-1 antibody dosage required mice. Importantly, completed phase 1 clinical trial combined regimen showed promising efficacy, exhibiting type I IFN induction, manageable safety revived immunotherapy most advanced metastatic solid propose this combination strategy warrants further translation.

Language: Английский

Citations

650
ImmunoPET: Concept, Design, and Applications DOI
Weijun Wei, Zachary T. Rosenkrans, Jianjun Liu

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(8), P. 3787 - 3851

Published: March 23, 2020

Immuno-positron emission tomography (immunoPET) is a paradigm-shifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and inherent sensitivity PET technique. A variety radionuclides mAbs have been exploited to develop immunoPET probes, which has driven by development optimization radiochemistry conjugation strategies. In addition, tumor-targeting vectors with short circulation time (e.g., Nanobody) or an enhanced binding affinity bispecific antibody) are being used design novel probes. Accordingly, several such as

Language: Английский

Citations

373
Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends DOI Creative Commons
Qian Sun, Zhenya Hong, Cong Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Language: Английский

Citations

250
Understanding and treating the inflammatory adverse events of cancer immunotherapy DOI Creative Commons
Michael Dougan, Adrienne Luoma, Stephanie K. Dougan

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(6), P. 1575 - 1588

Published: March 1, 2021

Language: Английский

Citations

212
AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review DOI Open Access
Michael Dougan, Yinghong Wang, Alberto Rubio–Tapia

et al.

Gastroenterology, Journal Year: 2020, Volume and Issue: 160(4), P. 1384 - 1393

Published: Oct. 17, 2020

Language: Английский

Citations

195
Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies DOI
Ryan J. Sullivan, Jeffrey S. Weber

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 21(7), P. 495 - 508

Published: July 27, 2021

Language: Английский

Citations

194
Emerging photodynamic nanotherapeutics for inducing immunogenic cell death and potentiating cancer immunotherapy DOI
Shenwu Zhang, Jing Wang,

Zhiqiang Kong

et al.

Biomaterials, Journal Year: 2022, Volume and Issue: 282, P. 121433 - 121433

Published: Feb. 19, 2022

Language: Английский

Citations

188
Biological drug and drug delivery-mediated immunotherapy DOI Creative Commons
Qingqing Xiao, Xiaotong Li, Yi Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 11(4), P. 941 - 960

Published: Dec. 31, 2020

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these whereas usage immunomodulators always limited by various factors such as susceptibility digestion enzymes in vivo, poor penetration across biological barriers, rapid clearance reticuloendothelial Drug delivery strategies potent promote their delivery. Herein, we reviewed potential targets for discussed biologics drug systems involved immunotherapy, particularly highlighted approved therapy tactics, finally offer perspectives this field.

Language: Английский

Citations

157