TRAIL-induced cytokine production via NFKB2 pathway promotes neutrophil chemotaxis and immune suppression in triple negative breast cancers DOI
Manjari Kundu, Yoshimi Endo Greer, Alexei Lobanov

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic that induces apoptosis in cells while sparing the non-malignant preclinical models. However, its efficacy clinical trials has been limited, suggesting unknown modulatory mechanisms responsible for lack of TRAIL activity patients. Here, we hypothesized treatment elicits transcriptional changes triple negative breast (TNBC) alter immune milieu. To test this, performed an RNAseq analysis MDA-MB-231 treated with TRAIL, followed by validation additional TNBC cell lines. significantly expression multiple cytokines such as CXCLs 1, 2, 3, 8,11 and IL-6, which are known to modify neutrophil function. Mechanistically, induction these was predominantly mediated death receptor 5, caspase 8 (but not enzymatic activity), non-canonical NFKB2 pathway. The produced TRAIL-treated enhanced chemotaxis healthy human donor isolated neutrophils.

Язык: Английский

Mucosal-associated invariant T-cells in pulmonary pathophysiology DOI Creative Commons

Jéssica Kamiki,

Carolina Mendonça Gorgulho, Joana R. Lérias

и другие.

Current Opinion in Pulmonary Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Purpose of review Mucosal-associated invariant T-cells (MAIT) have been associated with lung cancer and pulmonary infections. The treatment patients or infections includes host-directed therapies (HDTs). MAIT play a role in shaping the ‘milieu interne’ this addresses biology pathophysiology. Recent findings represent an attractive target for therapy malignancies are often difficult to exploit therapeutically due diversity both T-cell receptor (TCR) repertoire its ligandome. MAIT-cells restricted by major histocompatibility complex class I-related gene protein (MR1) that presents nondefined tumor-associated targets, bacterial products, vitamin drug derivates. Due their plasticity expression, able conversely switch from IFN-γ IL-17 production. Both cytokines key protective immune responses malignancies. MAIT-derived production interleukin (IL)-17/TGF-β shapes tumor micro-environment (TME), including tissue re-modelling leading fibrosis recruitment neutrophils. contribute gut-lung axis clinical improved checkpoint inhibition therapy. at crossroad HDTs targeting malignant infected cells. Clinical presentations overt inflammation, re-modeling reviewed along balance between Th1, Th2, Th9, Th17 immune-suppression Summary shape TME Drugs affect can be explored achieve results while curbing tissue-damaging responses.

Язык: Английский

Процитировано

0

The clinical landscape of CAR-engineered unconventional T cells DOI Creative Commons
Yan-Ruide Li, Yichen Zhu,

Yuning Chen

и другие.

Trends in cancer, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Unconventional T cells, such as invariant natural killer (iNKT), γδ T, and mucosal-associated (MAIT) play a pivotal role in bridging innate adaptive immunity. Their capacity for rapid tumor targeting effective modulation of the microenvironment (TME) makes them promising candidates cancer immunotherapy. Advances chimeric antigen receptor (CAR) engineering have further highlighted their therapeutic potential, particularly treating challenging cancers. Notably, these cells exhibit favorable safety profiles, enhancing viability off-the-shelf options. We provide comprehensive analysis clinical applications CAR-engineered unconventional focusing on genetic modifications, manufacturing processes, preconditioning regimens, dosing strategies. discuss successful examples from recent trials explore future directions utilizing therapy beyond.

Язык: Английский

Процитировано

0

TRAIL induces cytokine production via the NFkB2 pathway promoting neutrophil chemotaxis and neutrophil-mediated immune-suppression in triple negative breast cancer cells DOI Creative Commons
Manjari Kundu, Yoshimi Endo Greer, Alexei Lobanov

и другие.

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217692 - 217692

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

The microbiota shapes the life trajectory of mucosal-associated invariant T cells DOI Creative Commons
Yan-Ruide Li,

Xinyuan Shen,

Yichen Zhu

и другие.

Trends in Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

CD161 + CD127 + CD8 + T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus DOI Creative Commons
Jingjing Qu,

Yuekang Li,

Binggen Wu

и другие.

OncoImmunology, Год журнала: 2024, Номер 13(1)

Опубликована: Июнь 27, 2024

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function CD8+ subsets NSCLC diabetes. We recruited (n = 436) treated anti-PD-1 immunotherapy as first-line treatment. progression-free survival (PFS), overall (OS), infiltration, peripheral blood immunological characteristics were analyzed or without exhibited shorter PFS OS (p 0.0069 p 0.012, respectively) significantly lower infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage among CD8+T before treatment 0.0071) than that this trend continued after 0.0393). Flow multiple-immunofluorescence confirmed had to ratios RNA-sequencing analysis revealed immune-cytotoxic genes reduced subset compared CD161+CD127−CD8+ more cell-exhausted phenotypes ≥ 6.3% worse PFS. These findings indicate is risk factor for who undergo immunotherapy.CD161+CD127+CD8+ could be key indicator poor prognosis Our would help advancing therapy

Язык: Английский

Процитировано

3

Breaking the mold: Unconventional T cells in cancer therapy DOI
Yan-Ruide Li, Kuangyi Zhou, Yichen Zhu

и другие.

Cancer Cell, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

2

TRAIL-induced cytokine production via NFKB2 pathway promotes neutrophil chemotaxis and immune suppression in triple negative breast cancers DOI
Manjari Kundu, Yoshimi Endo Greer, Alexei Lobanov

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic that induces apoptosis in cells while sparing the non-malignant preclinical models. However, its efficacy clinical trials has been limited, suggesting unknown modulatory mechanisms responsible for lack of TRAIL activity patients. Here, we hypothesized treatment elicits transcriptional changes triple negative breast (TNBC) alter immune milieu. To test this, performed an RNAseq analysis MDA-MB-231 treated with TRAIL, followed by validation additional TNBC cell lines. significantly expression multiple cytokines such as CXCLs 1, 2, 3, 8,11 and IL-6, which are known to modify neutrophil function. Mechanistically, induction these was predominantly mediated death receptor 5, caspase 8 (but not enzymatic activity), non-canonical NFKB2 pathway. The produced TRAIL-treated enhanced chemotaxis healthy human donor isolated neutrophils.

Язык: Английский

Процитировано

1