Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors DOI Creative Commons
Gaurav Nayyar,

Yaya Chu,

Mitchell S. Cairo

et al.

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: Feb. 11, 2019

Despite advances in the diagnostic and therapeutic modalities, prognosis of several solid tumor malignancies remains poor. Different factors associated with tumors including a varied genetic signature, complex molecular signaling pathways, defective cross talk between cells immune cells, hypoxic immunosuppressive effects microenvironment result treatment resistant metastatic phenotype. Over past years, immunotherapy has emerged as an attractive option against multiple malignancies. The unique ability natural killer (NK) to target cancer without antigen specificity makes them ideal candidate for use tumors. However, outcomes adoptive NK cell infusions into patients have been disappointing. Extensive studies done investigate different strategies improve function, trafficking targeting. Use cytokines cytokine analogues well described utilized enhance proliferation, stimulation persistence cells. Other techniques like blocking human leukocyte antigen-killer receptors (KIR) interactions anti-KIR monoclonal antibodies, preventing CD16 receptor shedding, increasing expression activating NKG2D, immunocytokines checkpoint inhibitors can mediated cytotoxicity. Using genetically modified chimeric bispecific trispecific engagers, be effectively redirected improving their cytotoxic potential. In this review, we these highlighted need further optimize clinical outcome based

Language: Английский

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits DOI Creative Commons
Moritz Peiseler, Robert F. Schwabe, Jochen Hampe

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

Citations

312
Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome DOI Creative Commons
Chao Yang, Jason Siebert, Robert Burns

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 2, 2019

Abstract Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development heterogeneity of human NK yet be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct populations in bone marrow blood, including one population expressing higher levels immediate early genes indicative a homeostatic activation. Functionally matured with high expression CX3CR1 , HAVCR2 (TIM-3), ZEB2 represents terminally differentiated status unique transcriptional profile. Transcriptomic pseudotime analyses transitional between CD56 bright dim cells. Finally, donor GATA2 T354M mutation exhibits reduced percentage altered transcriptome elevated cell death. These data expand our understanding

Language: Английский

Citations

242
Killers 2.0: NK cell therapies at the forefront of cancer control DOI Open Access
Jonathan J. Hodgins, S. Khan, Maria M. Park

et al.

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(9), P. 3499 - 3510

Published: Sept. 2, 2019

Natural killer (NK) cells are innate cytotoxic lymphocytes involved in the surveillance and elimination of cancer. As we have learned more about mechanisms NK employ to recognize eliminate tumor cells, how, turn, cancer evades cell responses, gained a clear appreciation that can be harnessed immunotherapy. Here, review evidence for cells' critical role combating transformed malignant how immunotherapies potentiate responses therapeutic purposes. We highlight cutting-edge immunotherapeutic strategies preclinical clinical development such as adoptive transfer, chimeric antigen receptor-expressing (CAR-NKs), bispecific trispecific engagers (BiKEs TriKEs), checkpoint blockade, oncolytic virotherapy. Further, describe challenges face (e.g., postsurgical dysfunction) must overcome by these modalities achieve clearance.

Language: Английский

Citations

187
DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy DOI Open Access

Beatriz Sánchez-Correa,

Isabel Valhondo,

Fakhri Hassouneh

et al.

Cancers, Journal Year: 2019, Volume and Issue: 11(6), P. 877 - 877

Published: June 23, 2019

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in destruction tumor cells. Activation NK depend on a fine balance between activating and inhibitory signals mediated different receptors. In recent years, family paired receptors that interact with ligands Nectin/Nectin-like (Necl) has attracted great interest. Two these ligands, Necl-5 (usually termed CD155 or PVR) Nectin-2 (CD112), frequently expressed types cells, recognized group T exert opposite functions after interacting ligands. These include DNAM-1 (CD226), TIGIT, TACTILE (CD96) recently described PVRIG. Whereas activation through recognition CD112 enhances cell-mediated cytotoxicity against wide range TIGIT exerts an effect diminishing IFN-γ production, as well cytotoxicity. PVRIG also been identified receptor recognizes but not CD155. However, little is known about modulator responses humans. control growth metastases reported murine models, it suggested negatively regulates anti-tumor DNAM-1. from patients solid cancer leukemia, observed decreased expression may shift favor to PVRIG, further contributing diminished cytotoxic capacity patients. Analysis DNAM-1, human leukemia will clarify surveillance. Overall, can be speculated TIGIT/PVRIG pathways upregulated represent novel targets for checkpoint blockade immunotherapy.

Language: Английский

Citations

183
Diversity of peripheral blood human NK cells identified by single-cell RNA sequencing DOI Creative Commons
Samantha Smith, Philippa R Kennedy, Kevin Stacey

et al.

Blood Advances, Journal Year: 2020, Volume and Issue: 4(7), P. 1388 - 1406

Published: April 9, 2020

Abstract Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing NK cells, comparing gene expression unstimulated interleukin (IL)-2–activated from healthy cytomegalovirus (CMV)-negative donors. Three cell resembled well-described populations; CD56brightCD16−, CD56dimCD16+CD57−, CD56dimCD16+CD57+. CD56dimCD16+CD57− subdivided to include population with higher chemokine mRNA increased frequency killer-cell immunoglobulin-like receptor expression. novel human populations were identified: type I interferon–responding that CD56neg; exhibiting cytokine-induced memory-like phenotype, including granzyme B response IL-2; finally, small population, low ribosomal expression, downregulation oxidative phosphorylation, high levels immediate early genes indicative cellular activation. Analysis CMV+ donors established CMV altered the proportion each subset, especially an increase adaptive as well regulation within subset. Together, these data establish unexpected diversity provide new framework for analyzing responses health disease.

Language: Английский

Citations

179
COVID-19 and Obesity: Dangerous Liaisons DOI Open Access
Grazia Caci, Adriana Albini, Mario Malerba

et al.

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(8), P. 2511 - 2511

Published: Aug. 4, 2020

Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk severe disease fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) (COVID-19), there is now emerging evidence that overweight obesity predispose symptoms negative prognosis. Remarkably, severity COVID-19 appears rise with increasing body mass index (BMI). The association between outcomes overweight/obesity has biological physiological plausibility. Potential pathophysiological mechanisms may explain this strong include chronic pro-inflammatory state, excessive oxidative stress response, impaired immunity commonly reported in these individuals. role cytokines, mammalian target rapamycin (mTOR), altered natural killer cell polarization dangerous liaison are discussed here. These pathways can favor accelerate deleterious downstream cellular effects SARS-CoV-2. Moreover, well known be associated reduced lung function poor response mechanical ventilation, thus placing individuals at high illness mortality COVID-19. Furthermore, lead other complications, such renal failure, cardiovascular dysfunction, hypertension, vascular damage, which turn further clinical Obese should shielded against any potential viral exposure SARS-CoV-2 consequential considerations for compulsory protection devices social distancing. Health care providers aware predisposes prognosis patients.

Language: Английский

Citations

176
Subsets of ILC3−ILC1-like cells generate a diversity spectrum of innate lymphoid cells in human mucosal tissues DOI
Marina Cella, Ramya Gamini, Cristiane Sécca

et al.

Nature Immunology, Journal Year: 2019, Volume and Issue: 20(8), P. 980 - 991

Published: June 17, 2019

Language: Английский

Citations

171
A pan-cancer single-cell panorama of human natural killer cells DOI Creative Commons
Fei Tang, Jinhu Li, Lu Qi

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(19), P. 4235 - 4251.e20

Published: Aug. 21, 2023

Natural killer (NK) cells play indispensable roles in innate immune responses against tumor progression. To depict their phenotypic and functional diversities the microenvironment, we perform integrative single-cell RNA sequencing analyses on NK from 716 patients with cancer, covering 24 cancer types. We observed heterogeneity cell composition a tumor-type-specific manner. Notably, have identified group of tumor-associated that are enriched tumors, show impaired anti-tumor functions, associated unfavorable prognosis resistance to immunotherapy. Specific myeloid subpopulations, particular LAMP3+ dendritic cells, appear mediate regulation immunity. Our study provides insights into NK-cell-based immunity highlights potential clinical utilities subsets as therapeutic targets.

Language: Английский

Citations

171
Integrated longitudinal immunophenotypic, transcriptional, and repertoire analyses delineate immune responses in patients with COVID-19 DOI Creative Commons
Samuele Notarbartolo, Valeria Ranzani, Alessandra Bandera

et al.

Science Immunology, Journal Year: 2021, Volume and Issue: 6(62)

Published: Aug. 10, 2021

Characterization of the immune responses to SARS-CoV-2 reveals a CD8 + T cell subset that likely establishes memory virus.

Language: Английский

Citations

159
Natural killer cell therapies DOI
Éric Vivier, Lucas Rebuffet, Émilie Narni-Mancinelli

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8000), P. 727 - 736

Published: Feb. 21, 2024

Language: Английский

Citations

157