Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy DOI Creative Commons
X. Xia, Zongxin Yang,

Qisi Lu

et al.

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

Published: Aug. 26, 2024

In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment tumors affects cells, limiting treatment's effectiveness and safety. Therefore, enhancing cell infiltration capacity resolving responses within could boost anti-tumor effect. Specific strategies include structurally altering combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring status is beneficial in investigating viability such advancing therapy.

Language: Английский

T cells in health and disease DOI Creative Commons
Lina Sun, Yanhong Su, Anjun Jiao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 19, 2023

T cells are crucial for immune functions to maintain health and prevent disease. cell development occurs in a stepwise process the thymus mainly generates CD4

Language: Английский

Citations

359
Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer DOI Creative Commons
Briana G. Nixon, Fengshen Kuo, Liangliang Ji

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(11), P. 2044 - 2058.e5

Published: Oct. 25, 2022

Language: Английский

Citations

115
Nanomaterials in tumor immunotherapy: new strategies and challenges DOI Creative Commons
Xudong Zhu, Shenglong Li

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 13, 2023

Abstract Tumor immunotherapy exerts its anti-tumor effects by stimulating and enhancing immune responses of the body. It has become another important modality therapy with significant clinical efficacy advantages compared to chemotherapy, radiotherapy targeted therapy. Although various kinds tumor immunotherapeutic drugs have emerged, challenges faced in delivery these drugs, such as poor permeability low cell uptake rate, had prevented their widespread application. Recently, nanomaterials emerged a means for treatment different diseases due targeting properties, biocompatibility functionalities. Moreover, possess characteristics that overcome defects traditional immunotherapy, large drug loading capacity, precise easy modification, thus leading wide application immunotherapy. There are two main classes novel nanoparticles mentioned this review: organic (polymeric nanomaterials, liposomes lipid nanoparticles) inorganic (non-metallic metallic nanomaterials). Besides, fabrication method nanoparticles, Nanoemulsions, was also introduced. In summary, review article mainly discussed research progress based on past few years offers theoretical basis exploring strategies future.

Language: Английский

Citations

110
Exosome-Mediated Immunosuppression in Tumor Microenvironments DOI Creative Commons

Qihui Xie,

Jiqi Zheng,

Jiayi Ding

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1946 - 1946

Published: June 16, 2022

Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to recipient cells and involved in multiple physiopathological processes, including immunoregulation. Our pioneering study revealed that cancer release programmed death-ligand 1-positive into the circulation counter antitumor immunity systemically via T cells. Tumor cell-derived (TDEs) also play an immunosuppressive role other immunocytes, dendritic (DCs), macrophages, natural killer (NK) cells, myeloid-derived suppressor (MDSCs). Moreover, nontumor tumor microenvironments (TMEs) exert effects. This review systematically provides a summary of immunosuppression induced microenvironments, which modulates growth, invasion, metastasis, immunotherapeutic resistance. Additionally, therapeutic strategies targeting molecular mechanism exosome-mediated development, may help overcome several obstacles, such as immune tolerance oncotherapy, discussed. Detailed knowledge specific functions contribute development innovative treatments.

Language: Английский

Citations

87
Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development DOI Creative Commons
Weihua Yu, Yongmei Tu, Zi Long

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 22

Published: June 28, 2022

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between tumorigenesis. However, mechanisms driving development of persistent toward tumorigenesis remain unclear. In this study, we assess potential role reactive oxygen species (ROS) associated in modulating inflammation-induced Recent reports have emphasized cross-talk oxidative stress many pathological processes. Exposure carcinogenic hazards may lead damage, which further stimulates infiltration various types inflammatory cells. turn, increased cytokine chemokine release from cells promotes ROS production lesions, even absence hazardous stimuli. Moreover, not only DNA damage but also participate cell proliferation, differentiation, apoptosis by several transcription factors signaling pathways. We summarize how changes redox state trigger lesions into tumors. Generally, cancer require an appropriate microenvironment support their growth, spread, metastasis, provide necessary catalyst for inflammation-driven cancer. conclusion, bridge gap development; therefore, targeting represents a new avenue prevention treatment

Language: Английский

Citations

76
T cell exhaustion in malignant gliomas DOI Creative Commons
Matthew B. Watowich, Mark R. Gilbert, Mioara Larion

et al.

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(4), P. 270 - 292

Published: Jan. 20, 2023

Despite advances in understanding tumor biology, malignant gliomas remain incurable. While immunotherapy has improved outcomes other cancer types, comparable efficacy not yet been demonstrated for primary cancers of the central nervous system (CNS). T cell exhaustion, defined as a progressive decrease effector function, sustained expression inhibitory receptors, metabolic dysfunction, and distinct epigenetic transcriptional alterations, contributes to failure CNS. Herein, we describe recent drivers exhaustion glioma microenvironment. We discuss extrinsic intrinsic factors that contribute highlight potential avenues reversing this phenotype. Our ability directly target specific immunosuppressive brain would be major advance immunotherapy.

Language: Английский

Citations

58
Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma DOI Creative Commons
Juyeun Lee, Michael Nicosia, Ellen S. Hong

et al.

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(9), P. 2090 - 2105

Published: June 28, 2023

Abstract Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, emerging evidence suggests that these extend to genetic/epigenetic cellular differences, including immune responses. However, the mechanisms driving immunologic sex not fully understood. Here, we demonstrate T cells play a critical role GBM differences. Male mice exhibited accelerated tumor growth, with decreased frequency increased exhaustion of CD8+ tumor. Furthermore, higher progenitor exhausted was found males, improved responsiveness anti–PD-1 treatment. Moreover, T-cell observed male patients. Bone marrow chimera adoptive transfer models indicated cell–mediated control predominantly regulated cell-intrinsic manner, partially mediated by X chromosome inactivation escape gene Kdm6a. These findings sex-biased predetermined behavior is for inducing progression immunotherapy response. Significance: Immunotherapies patients have been unsuccessful due variety factors, highly immunosuppressive microenvironment GBM. This study demonstrates behaviors intrinsically regulated, further suggesting sex-specific approaches can be leveraged potentially improve therapeutic efficacy See related commentary Alspach, p. 1966. article featured Selected Articles from Issue, 1949

Language: Английский

Citations

56
Identification of the novel exhausted T cell CD8 + markers in breast cancer DOI Creative Commons
Hengrui Liu,

Angela Dong,

Ayana Meegol Rasteh

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 19, 2024

Cancer is one of the most concerning public health issues and breast cancer common cancers in world. The immune cells within tumor microenvironment regulate development. In this study, single cell data sets were used to identify marker gene for exhausted CD8 + T (CD8Tex) cancer. Machine learning methods cluster subtypes establish prognostic models with bulk using evaluate impacts CD8Tex. We analyzed overexpressing survival-associated genes identified CD8Tex hub protein-protein-interaction network. relevance T-cells was evaluated. clinical associations sequencing spatial data. pan-cancer expression, survival, association analyzed. biomarker CD8Tex-based subtyping systems performed well separation patients different survival. CRTAM, CLEC2D, KLRB1 as demonstrated have potential therapy impact. This study provides a unique view critical therapy.

Language: Английский

Citations

44
Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

Citations

44
Roles of reactive oxygen species in inflammation and cancer DOI Creative Commons

Yunfei Yu,

Shengzhuo Liu,

Luchen Yang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: April 1, 2024

Abstract Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions ROS equilibrium span various diseases, and current insights suggest dual role for tumorigenesis the immune response within cancer. This review rigorously examines production its normal cells, elucidating subsequent regulatory network inflammation Comprehensive synthesis details documented impacts on diverse cells. Exploring intricate relationship between cancer immunity, we highlight influence existing immunotherapies, including checkpoint blockade, chimeric antigen receptors, vaccines. Additionally, underscore promising prospects utilizing targeting modulators as novel immunotherapeutic interventions discusses complex interplay ROS, inflammation, tumorigenesis, emphasizing multifaceted functions both physiological conditions. It also underscores potential implications immunotherapy suggests future research directions, development targeted therapies precision oncology approaches. In summary, this emphasizes significance understanding ROS‐mediated mechanisms advancing therapy developing personalized treatments.

Language: Английский

Citations

30