T cell senescence: a new perspective on immunotherapy in lung cancer DOI Creative Commons

Mengge Huang,

Yuetong Wang,

Liguang Fang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 13, 2024

T cell senescence is an indication of dysfunction. The ability senescent cells to respond cognate antigens reduced and they are in the late stage differentiation proliferation; therefore, cannot recognize eliminate tumor a timely effective manner, leading formation suppressive microenvironment. Establishing methods reverse particularly important for immunotherapy. Aging exacerbates profound changes immune system, increased susceptibility chronic, infectious, autoimmune diseases. Patients with malignant lung tumors have impaired function high risk recurrence, metastasis, mortality. Immunotherapy based on PD-1, PD-L1, CTLA-4, other checkpoints promising treating malignancies. However, can lead low efficacy or unsuccessful treatment results some immunotherapies. Efficiently blocking reversing key goal enhancement This study discusses characteristics, mechanism, expression strategies.

Language: Английский

Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer DOI Creative Commons
Hao Zhang, Ziyu Dai,

Wantao Wu

et al.

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

Published: June 4, 2021

Abstract The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ cell death-ligand (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T function during different phases of T-cell activation. Inhibitors targeting CTLA-4/B7 PD1/PD-L1 pathways have revolutionized immunotherapies for numerous cancer types. Although the combined anti-CTLA-4/B7 anti-PD1/PD-L1 therapy has demonstrated promising clinical efficacy, only a small percentage patients receiving or experienced prolonged survival. Regulation expression PD-L1 CTLA-4 significantly impacts treatment effect. Understanding in-depth mechanisms interplays could help identify with better immunotherapy responses promote their care. In this review, regulation is discussed at levels DNA, RNA, proteins, as well indirect biomarkers, localization within cell, drugs. Specifically, some potential drugs been developed to expressions high efficiency.

Language: Английский

Citations

353
NF‐κB signaling in inflammation and cancer DOI
Tao Zhang, Chao Ma, Zhiqiang Zhang

et al.

MedComm, Journal Year: 2021, Volume and Issue: 2(4), P. 618 - 653

Published: Dec. 1, 2021

Abstract Since nuclear factor of κ‐light chain enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism NF‐κB for 35 years, which lead significant progress. Meanwhile, molecular mechanisms activation also illuminated, cascades signaling events leading activity key components pathway are identified. It has suggested plays an important role human diseases, especially inflammation‐related diseases. These studies make attractive target disease treatment. This review aims summarize knowledge family members NF‐κB, as well basic activation. We will effects dysregulated on inflammation, tumorigenesis, tumor microenvironment. The progression translational study drug development targeting inflammatory diseases cancer treatment potential obstacles be discussed. Further investigations precise functions physiological pathological settings underlying urgent need develop drugs treatment, with minimal side effects.

Language: Английский

Citations

287
Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα DOI Creative Commons
Dong Guo, Yingying Tong, Xiaoming Jiang

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(9), P. 1312 - 1324.e6

Published: Aug. 24, 2022

Language: Английский

Citations

215
The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases DOI Creative Commons
Lorenzo Cuollo, Fabrizio Antonangeli, Angela Santoni

et al.

Biology, Journal Year: 2020, Volume and Issue: 9(12), P. 485 - 485

Published: Dec. 21, 2020

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state stable proliferative arrest is accompanied by Senescence-Associated Secretory Phenotype (SASP), which entails copious secretion proinflammatory signals in tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with use senolytics abolishing SASP without killing cell so-called “senomorphics”. In addition, recent works demonstrate possibility modifying composition secretome genetic pharmacological intervention. The purpose not renounce potent immunostimulatory nature SASP, but rather learning modulate it for combating cancer other diseases. This review describes main molecular mechanisms regulating reports evidence feasibility abrogating modulating discussing possible implications both strategies.

Language: Английский

Citations

202
Hypoxia as a driver of resistance to immunotherapy DOI
Joanna Kopecka, Iris C. Salaroglio, Elisabeth Pérez-Ruíz

et al.

Drug Resistance Updates, Journal Year: 2021, Volume and Issue: 59, P. 100787 - 100787

Published: Nov. 18, 2021

Language: Английский

Citations

174
Inflammation-Induced Tumorigenesis and Metastasis DOI Open Access
Sana Hibino, Tetsuro Kawazoe, Hidenori Kasahara

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5421 - 5421

Published: May 21, 2021

Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms is now recognized as hallmark of cancer an attractive therapeutic target cancer. In this review, we discuss recent advances molecular how inflammation promotes suppresses anti-tumor immunity types solid tumors, including esophageal, gastric, colorectal, liver, pancreatic well hematopoietic malignancies.

Language: Английский

Citations

172
Mechanisms driving the immunoregulatory function of cancer cells DOI
Antoinette van Weverwijk, Karin E. de Visser

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 193 - 215

Published: Jan. 30, 2023

Language: Английский

Citations

145
Regulatory mechanisms of PD-1/PD-L1 in cancers DOI Creative Commons
Xin Lin,

Kuan Kang,

Pan Chen

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 18, 2024

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) cell ligands (PD-Ls) are considered be major molecules. interaction of PD-1 PD-L1 negatively regulates adaptive response mainly by inhibiting activity effector T while enhancing function regulatory (Tregs), largely contributing maintenance homeostasis prevents dysregulated immunity harmful responses. However, exploit PD-1/PD-L1 axis cause escape in development Blockade neutralizing antibodies restores enhances anti-tumor immunity, achieving remarkable success therapy. Therefore, mechanisms cancers attracted an increasing attention. This article aims provide a comprehensive review roles signaling human autoimmune diseases cancers. We summarize all aspects underlying expression cancers, including genetic, epigenetic, post-transcriptional post-translational mechanisms. In addition, we further progress clinical research on antitumor effects targeting alone combination with other therapeutic approaches, providing new strategies for finding tumor markers developing combined approaches.

Language: Английский

Citations

111
Epstein–Barr Virus–Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1 DOI Creative Commons

Junshang Ge,

Jie Wang, Fang Xiong

et al.

Cancer Research, Journal Year: 2021, Volume and Issue: 81(19), P. 5074 - 5088

Published: July 28, 2021

Epstein-Barr virus (EBV) infection is an established cause of nasopharyngeal carcinoma (NPC) and involved in a variety malignant phenotypes, including tumor immune escape. EBV can encode circular RNAs (circRNA), however, little known regarding the biological functions these circRNAs NPC. In this study, EBV-encoded circBART2.2 was found to be highly expressed NPC where it upregulated PD-L1 expression inhibited T-cell function vitro vivo. promoted transcription by binding helicase domain RIG-I activating factors IRF3 NF-κB, resulting These results elucidate circBART2.2, explain novel mechanism escape caused infection, provide new immunotherapy target for treating SIGNIFICANCE: This work demonstrates that essential regulation subsequent carcinoma.

Language: Английский

Citations

108
Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2 DOI Creative Commons
Manon Venet, Margarida Sá Ribeiro, Élodie Décembre

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 8, 2023

Type I and III interferons (IFN-I/λ) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range by pDCs requires sustained integrin-mediated cell adhesion with infected In turn, restrict viral spread an response directed toward This specialized function enables to efficiently turn-off replication, likely via a local at contact site By exploring pDC in patients, further responsiveness inversely correlates severity disease. The is particularly impaired severe COVID-19 patients. Overall, propose activation essential control SARS-CoV-2-infection. Failure develop could be understand cases COVID-19.

Language: Английский

Citations

42