CD56 does not contribute to the anti-tumor, tissue homing, and glycolytic capacity of human NK cells DOI
Ana L. Portillo,

Eduardo A. Peña Rojas,

Misaal Mehboob

et al.

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract Natural killer (NK) cells are critical innate immune involved in the clearance of virally infected and malignant cells. Human NK distinguished by their surface expression CD56 a lack CD3. While cell density has long been used as prototypic marker to characterize primary human functional subsets, exact role is still not fully understood. Here, we eliminated ex vivo expanded (CD56bright) using CRISPR/Cas9 order assess function this highly activated cytotoxic population. We show that no effect on proliferative capacity or various activation inhibitory markers. Further, does contribute cell–mediated cytotoxicity, inflammatory cytokine production, ability control tumor engraftment vivo. also found while deletion did impact glycolytic metabolism, it increase reliance oxidative phosphorylation. Last, alter tissue trafficking. Our results indicate could be hyperfunctional state cells, directly influence antitumor functions

Language: Английский

Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy DOI Creative Commons
Md. Ataur Rahman,

Mahesh Kumar Yadab,

Meser M. Ali

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924

Published: Nov. 20, 2024

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.

Language: Английский

Citations

8
Metabolism: Fine and Coarse Controls DOI
Sameh S. M. Soliman, Rania Hamdy,

Mohamed I. Husseiny

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Dysregulated glutathione metabolism impairs natural killer cell function in patients with acute leukemia DOI
Yue Zhao, Yan Wang, Tingting Liang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114566 - 114566

Published: April 12, 2025

Language: Английский

Citations

0
Recent advances in understanding the immune microenvironment in ovarian cancer DOI Creative Commons
Jinxin Chen, Lu Yang, Yiming Ma

et al.

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

Published: June 5, 2024

The occurrence of ovarian cancer (OC) is a major factor in women’s mortality rates. Despite progress medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. tumor microenvironment (TME) includes cells, fibroblasts linked to (CAFs), immune-inflammatory and the substances these cells secrete, along with non-cellular components extracellular matrix (ECM). First, TME mainly plays role inhibiting growth protecting normal cell survival. As tumors progress, gradually becomes place promote progression. Immune have attracted much attention as targets immunotherapy. checkpoint inhibitor (ICI) therapy has potential regulate TME, suppressing factors that facilitate advancement, reactivating immune managing growth, extending advanced cancer. This review presents an outline current studies on distinct cellular elements within detailing their main functions possible signaling pathways. Additionally, we examine immunotherapy rechallenge OC, specific emphasis biological reasons behind resistance ICIs.

Language: Английский

Citations

3
High-throughput screening for optimizing adoptive T cell therapies DOI Creative Commons
Yuchen Zhang,

Qinglong Xu,

Zhifei Gao

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Nov. 13, 2024

Abstract Adoptive T cell therapy is a pivotal strategy in cancer immunotherapy, demonstrating potent clinical efficacy. However, its limited durability often results primary resistance. High-throughput screening technologies, which include both genetic and non-genetic approaches, facilitate the optimization of adoptive therapies by enabling selection biologically significant targets or substances from extensive libraries. In this review, we examine advancements high-throughput technologies their applications therapies. We highlight use for cells, tumor other promising combination strategies, elucidate role identifying small molecules targeted delivery systems relevant to therapies, providing guidance future research applications.

Language: Английский

Citations

2
Innate immunity—With an adaptive twist DOI
Steven Z. Josefowicz, Joseph C. Sun

Immunological Reviews, Journal Year: 2024, Volume and Issue: 323(1), P. 5 - 7

Published: April 17, 2024

Language: Английский

Citations

1
Mesenchymal Stem/Stromal cells in solid tumor Microenvironment: Orchestrating NK cell remodeling and therapeutic insights DOI
Hao Zhang, Xiaoli Cao,

Rulin Gui

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113181 - 113181

Published: Sept. 20, 2024

Language: Английский

Citations

1
CD56 does not contribute to the anti-tumor, tissue homing, and glycolytic capacity of human NK cells DOI
Ana L. Portillo,

Eduardo A. Peña Rojas,

Misaal Mehboob

et al.

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract Natural killer (NK) cells are critical innate immune involved in the clearance of virally infected and malignant cells. Human NK distinguished by their surface expression CD56 a lack CD3. While cell density has long been used as prototypic marker to characterize primary human functional subsets, exact role is still not fully understood. Here, we eliminated ex vivo expanded (CD56bright) using CRISPR/Cas9 order assess function this highly activated cytotoxic population. We show that no effect on proliferative capacity or various activation inhibitory markers. Further, does contribute cell–mediated cytotoxicity, inflammatory cytokine production, ability control tumor engraftment vivo. also found while deletion did impact glycolytic metabolism, it increase reliance oxidative phosphorylation. Last, alter tissue trafficking. Our results indicate could be hyperfunctional state cells, directly influence antitumor functions

Language: Английский

Citations

0