CD8+ T Cell Exhaustion in Cancer DOI Creative Commons
Joseph S. Dolina, Natalija Budimir, Graham D. Thomas

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 20, 2021

A paradigm shift in the understanding of exhausted CD8 + T cell (T ex ) lineage is underway. Originally thought to be a uniform population that progressively loses effector function response persistent antigen, single-cell analysis has now revealed composed multiple interconnected subpopulations. The heterogeneity within comprised immune checkpoint blockade (ICB) permissive and refractory subsets termed stem-like terminally differentiated cells, respectively. These populations occupy distinct peripheral intratumoral niches are characterized by transcriptional processes govern transitions between states. This review presents key findings field construct an updated view spatial, transcriptional, functional anti-tumoral . emerging insights broadly call for (re-)focusing cancer immunotherapies center on driver mechanism(s) underlying developmental continuum aimed at stabilizing subsets.

Language: Английский

Regulation and Function of the PD-L1 Checkpoint DOI Creative Commons
Chong Sun, Riccardo Mezzadra, Ton N. Schumacher

et al.

Immunity, Journal Year: 2018, Volume and Issue: 48(3), P. 434 - 452

Published: March 1, 2018

Language: Английский

Citations

1825
Inflammation and tumor progression: signaling pathways and targeted intervention DOI Creative Commons

Huakan Zhao,

Lei Wu,

Guifang Yan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 12, 2021

Abstract Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates progression treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation dendritic cells (DCs) antigen presentation, leading anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers activators transcription (JAK-STAT), toll-like receptor (TLR) cGAS/STING, mitogen-activated protein kinase (MAPK); factors, including cytokines (e.g., interleukin (IL), interferon (IFN), necrosis (TNF)-α), chemokines C-C motif chemokine ligands (CCLs) C-X-C (CXCLs)), growth factors vascular endothelial (VEGF), transforming (TGF)-β), inflammasome; well metabolites prostaglandins, leukotrienes, thromboxane, specialized proresolving mediators (SPM), have been identified pivotal regulators initiation resolution inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, SPM developed specifically modulate in cancer therapy, with some these already undergoing clinical trials. Herein, we discuss crosstalk between processes. We also highlight potential targets for harnessing cancer.

Language: Английский

Citations

1636
Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade DOI
Brian C. Miller, Debattama R. Sen, Rose Al Abosy

et al.

Nature Immunology, Journal Year: 2019, Volume and Issue: 20(3), P. 326 - 336

Published: Feb. 18, 2019

Language: Английский

Citations

1549
Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives DOI Creative Commons

Xiaoqi Mao,

Jin Xu, Wei Wang

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Oct. 11, 2021

Abstract Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote growth, angiogenesis, invasion metastasis, along extracellular matrix (ECM) remodeling even chemoresistance. Numerous previous studies have confirmed critical role interaction between cells in tumorigenesis development. However, recently, mutual effects immune (TIME) been identified as another key factor promoting progression. The TIME mainly consists distinct populations islets is highly associated antitumor immunological state TME. interact tumor-infiltrating well other within via secretion various cytokines, growth factors, chemokines, exosomes effector molecules, consequently shaping an immunosuppressive TME that enables cancer to evade surveillance system. In-depth interactions, particularly complicated mechanisms connecting cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding direct indirect crosstalk infiltrating further summarize possible immunoinhibitory induced by In addition, present current related CAF-targeting immunotherapies briefly describe some future perspectives CAF research end.

Language: Английский

Citations

1420
CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review DOI
Bagher Farhood, Masoud Najafi, Keywan Mortezaee

et al.

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(6), P. 8509 - 8521

Published: Nov. 22, 2018

CD8+ cytotoxic T lymphocytes (CTLs) are preferred immune cells for targeting cancer. During cancer progression, CTLs encounter dysfunction and exhaustion due to immunerelated tolerance immunosuppression within the tumor microenvironment (TME), with all favor adaptive immune-resistance. Cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, regulatory (Tregs) could make immunologic barriers against CD8 + cell-mediated antitumor responses. Thus, needed be primed activated toward effector in a process called immunity cycle making durable efficient The cell priming is directed essentially as corroboration work between of innate including dendritic (DCs) natural killer (NK) CD4 adoptive immunity. Upon activation, infiltrate core or invading site (so-called infiltrated-inflamed [I-I] TME) take essential roles killing cells. Exogenous reactivation and/or can possible using rational immunotherapy strategies. increase ratio costimulatory coinhibitory mediators checkpoint blockade (ICB) approach. Programmed death-1 receptor (PD-1)-ligand (PD-L1) CTL-associated antigen 4 (CTLA-4) receptors that targeted relieving renewing their priming, respectively, thereby eliminating antigen-expressing Due diverse relation Tregs, Treg activity dampened increasing number rescuing functional potential induce immunosensitivity

Language: Английский

Citations

1321
Cytotoxic CD8+ T cells in cancer and cancer immunotherapy DOI Creative Commons
Hans Raskov, Adile Orhan, Jan Pravsgaard Christensen

et al.

British Journal of Cancer, Journal Year: 2020, Volume and Issue: 124(2), P. 359 - 367

Published: Sept. 15, 2020

Abstract The functions of, and interactions between, the innate adaptive immune systems are vital for anticancer immunity. Cytotoxic T cells expressing cell-surface CD8 most powerful effectors in response form backbone of current successful cancer immunotherapies. Immune-checkpoint inhibitors designed to target immune-inhibitory receptors that function regulate response, whereas adoptive cell-transfer therapies use + with genetically modified receptors—chimaeric antigen receptors—to specify enhance T-cell functionality. New generations cytotoxic or synthetic being developed evaluated clinical trials. Furthermore, combinatory regimens might optimise treatment effects reduce adverse events. This review summarises advances research on prominent immunotherapy, cells, discusses possible implications future treatment.

Language: Английский

Citations

1107
Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma DOI Creative Commons

Hanjie Li,

Anne M. van der Leun, Ido Yofe

et al.

Cell, Journal Year: 2018, Volume and Issue: 176(4), P. 775 - 789.e18

Published: Dec. 27, 2018

Language: Английский

Citations

943
‘Off-the-shelf’ allogeneic CAR T cells: development and challenges DOI Open Access
Stéphane Depil, Philippe Duchâteau, Stephan A. Grupp

et al.

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(3), P. 185 - 199

Published: Jan. 3, 2020

Language: Английский

Citations

884
TOX is a critical regulator of tumour-specific T cell differentiation DOI
Andrew Scott, Friederike Dündar, Paul Zumbo

et al.

Nature, Journal Year: 2019, Volume and Issue: 571(7764), P. 270 - 274

Published: June 17, 2019

Language: Английский

Citations

883
Pan-cancer single-cell landscape of tumor-infiltrating T cells DOI
Liangtao Zheng, Shishang Qin, Wen Si

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6574)

Published: Dec. 16, 2021

T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics tumor-infiltrating across types. We built single-cell RNA-sequencing pan-cancer atlas for 316 donors 21 types revealed distinct cell composition patterns. found multiple state-transition paths exhaustion CD8+ preference those among different tumor Certain populations showed specific correlation with patient properties such as mutation burden, shedding light on possible determinants microenvironment. compositions within tumors alone could classify patients into groups clinical trait specificity, providing new insights immunity precision immunotherapy targeting cells.

Language: Английский

Citations

849