Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression DOI Creative Commons
Antonino Bruno, Lorenzo Mortara, Denisa Baci

et al.

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: April 18, 2019

Myeloid-derived suppressor cells (MDSCs) contribute to the induction of an immune suppressive/anergic, tumor permissive environment. MDSCs act as immunosuppression orchestrators also by interacting with several components both innate and adaptive immunity. Natural killer (NK) are lymphoid functioning primary effector immunity, against tumors virus-infected cells. Apart from previously described anergy hypo-functionality NK in different tumors, cancer patients show pro-angiogenic phenotype functions, similar decidual We termed present microenvironment: “tumor infiltrating NK” (TINKs), peripheral blood associated (TANKs). The contribution regulating cell function tumor-bearing host still represent a poorly explored topic, even less is known on regulation MDSCs. Here, we review whether crosstalk between can impact onset, angiogenesis progression, focusing relevant cellular molecular events. propose that similarity properties MDSC those decisual during pregnancy could hint possible onco-fetal origin these leukocytes.

Language: Английский

Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape DOI Creative Commons

Xianjie Jiang,

Jie Wang, Xiangying Deng

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Jan. 15, 2019

Tumor immune escape is an important strategy of tumor survival. There are many mechanisms escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway component can inhibit the activation T lymphocytes and enhance tolerance cells, thereby achieving escape. Therefore, targeting PD-L1/PD-1 attractive for cancer treatment; however, therapeutic effectiveness remains poor. This situation requires gaining deeper understanding complex varied molecular factors driving expression pathway. In this review, we summarize regulation microenvironment their roles mediating Overall, evidence accumulated to date suggests that induction PD-L1 by inflammatory may be one most affecting efficiency blocking.

Language: Английский

Citations

1160
Immune checkpoint signaling and cancer immunotherapy DOI Creative Commons
Xing He, Chenqi Xu

Cell Research, Journal Year: 2020, Volume and Issue: 30(8), P. 660 - 669

Published: May 28, 2020

Abstract Immune checkpoint blockade therapy has become a major weapon in fighting cancer. Antibody drugs, such as anti-PD-1 and anti-PD-L1, demonstrate obvious advantages broad applicability across cancer types durable clinical response when treatment is effective. However, the overall rates are still unsatisfying, especially for cancers with low mutational burden. Moreover, adverse effects, autoimmune symptoms tumor hyperprogression, present significant downside some applications. These challenges reflect urgent need to fully understand basic biology of immune checkpoints. In this review, we discuss regulation signaling at multiple levels provide an overview our current understanding biology. Topics include surface expression known proteins via delivery, internalization, recycling, degradation. Upon reaching surface, checkpoints engage both conventional trans also cis interactions ligands induce regulate responses. Novel therapeutic strategies targeting these pathways addition classical have recently emerged been tested preclinical models, providing new avenues developing next-generation immunotherapies.

Language: Английский

Citations

986
The updated landscape of tumor microenvironment and drug repurposing DOI Creative Commons

Ming-Zhu Jin,

Weilin Jin

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Aug. 25, 2020

Abstract Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram initiation, growth, invasion, metastasis, response to therapies. Cancer research treatment have switched from a cancer-centric model TME-centric one, considering the increasing significance of TME cancer biology. Nonetheless, clinical efficacy therapeutic strategies targeting TME, especially specific cells or pathways remains unsatisfactory. Classifying chemopathological characteristics crosstalk among one another greatly benefit further studies exploring effective treating methods. Herein, we present an updated image with emphasis on hypoxic niche, immune microenvironment, metabolism acidic innervated mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, statin new antitumor application. These are considered as viable candidates for combination therapy due their activity extensive use practice. also provide our outlook directions potential applications theory. This review depicts comprehensive vivid landscape biology treatment.

Language: Английский

Citations

893
Mechanisms Controlling PD-L1 Expression in Cancer DOI Creative Commons
Jong‐Ho Cha, Li-Chuan Chan, Chia‐Wei Li

et al.

Molecular Cell, Journal Year: 2019, Volume and Issue: 76(3), P. 359 - 370

Published: Oct. 24, 2019

Language: Английский

Citations

748
Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy DOI Creative Commons
Jackie E. Bader, Kelsey Voss, Jeffrey C. Rathmell

et al.

Molecular Cell, Journal Year: 2020, Volume and Issue: 78(6), P. 1019 - 1033

Published: June 1, 2020

Language: Английский

Citations

731
AMP-activated protein kinase: the current landscape for drug development DOI Open Access
Gregory R. Steinberg, David Carling

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(7), P. 527 - 551

Published: March 13, 2019

Language: Английский

Citations

561
New insights into activation and function of the AMPK DOI
Gregory R. Steinberg, D. Grahame Hardie

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(4), P. 255 - 272

Published: Oct. 31, 2022

Language: Английский

Citations

489
Regulation of PD-L1 expression in the tumor microenvironment DOI Creative Commons
Ming Yi,

Mengke Niu,

Linping Xu

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Jan. 7, 2021

Abstract Programmed death-ligand 1 (PD-L1) on cancer cells engages with programmed cell death-1 (PD-1) immune cells, contributing to escape. For multiple types, the PD-1/PD-L1 axis is major speed-limiting step of anti-cancer response. In this context, blocking could restore T from exhausted status and eradicate cells. However, only a subset PD-L1 positive patients benefits α-PD-1/PD-L1 therapies. Actually, expression regulated by various factors, leading diverse significances positivity. Understanding mechanisms regulation helpful select enhance treatment effect. review, we focused regulators at levels transcription, post-transcription, post-translation. Besides, discussed potential applications these laboratory findings in clinic.

Language: Английский

Citations

450
Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond DOI
Luoyan Ai, Antao Xu, Jie Xu

et al.

Advances in experimental medicine and biology, Journal Year: 2020, Volume and Issue: unknown, P. 33 - 59

Published: Jan. 1, 2020

Language: Английский

Citations

386
Pyroptosis: a new paradigm of cell death for fighting against cancer DOI Creative Commons
Yixin Tan,

Quanzhu Chen,

Xiaoling Li

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: May 3, 2021

Abstract Background Unraveling the mystery of cell death is one most fundamental progresses life sciences during past decades. Regulated (RCD) or programmed (PCD) not only essential in embryonic development, but also plays an important role occurrence and progression diseases, especially cancers. Escaping hallmarks cancer. Main body Pyroptosis inflammatory usually caused by microbial infection, accompanied activation inflammasomes maturation pro-inflammatory cytokines interleukin-1β (IL-1β) interleukin-18 (IL-18). Gasdermin family proteins are executors pyroptosis. Cytotoxic N-terminal gasdermins generated from caspases granzymes proteases mediated cleavage gasdermin oligomerizes forms pore across membrane, leading to release IL-1β, IL-18. exerts tumor suppression function evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy therapy, induce pyroptosis cancer, which potentiate local systemic immunity. On other hand, normal cells attributes side effects anti-cancer therapies. Conclusion In this review, we focus on regulatory mechanisms suppressive We discuss attribution reprogramming microenvironments restoration immunity its potential application cancer therapy.

Language: Английский

Citations

358