Tumor glucose metabolism and the T cell glycocalyx: implication for T cell function

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

Published: May 31, 2024

The T cell is an immune subset highly effective in eliminating cancer cells. Cancer immunotherapy empowers cells and occupies a solid position treatment. response rate, however, remains relatively low (<30%). efficacy of dependent on infiltration into the tumor microenvironment (TME) ability these infiltrated to sustain their function within TME. A better understanding inhibitory impact TME crucial improve immunotherapy. Tumor are well described for switch aerobic glycolysis (Warburg effect), resulting high glucose consumption metabolically distinct Conversely, glycosylation, predominant posttranslational modification proteins, also relies molecules. Proper glycosylation receptors influences immunological synapse between cells, thereby affecting effector functions including cytolytic cytostatic activities. This review delves complex interplay metabolism glycocalyx shedding light how can induce alterations glycocalyx, which subsequently influence cell's target eliminate

Language: Английский

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Targeting the “Sweet Side” of Tumor with Glycan-Binding Molecules Conjugated-Nanoparticles: Implications in Cancer Therapy and Diagnosis

Nanomaterials, Journal Year: 2021, Volume and Issue: 11(2), P. 289 - 289

Published: Jan. 22, 2021

Nanotechnology is in the spotlight of therapeutic innovation, with numerous advantages for tumor visualization and eradication. The end goal use nanoparticles, however, remains distant due to limitations nanoparticles target cancer tissue. functionalization nanosystem surfaces biological ligands a major strategy directing actions nanomaterials specifically cells. Cancer formation metastasis are accompanied by profound alterations protein glycosylation. Hence, detection targeting aberrant glycans great value diagnosis therapy. In this review, we provide brief update on recent progress glycosylation functionalizing glycan-binding molecules (with special focus lectins anti-glycan antibodies) improve efficacy targeting, diagnosis, therapy outline challenges implementing approach. We envision that combination nanotechnological strategies cancer-associated glycan could remodel field therapy, including immunotherapy.

Language: Английский

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Advances in the Immunomodulatory Properties of Glycoantigens in Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(8), P. 1854 - 1854

Published: April 7, 2022

Aberrant glycosylation in tumour progression is currently a topic of main interest. Tumour-associated carbohydrate antigens (TACAs) are expressed wide variety epithelial cancers, being both diagnostic tool and potential treatment target, as they have impact on patient outcome disease progression. Glycans affect tumour-cell biology properties well the antitumor immune response. It has been ascertained that TACAs cell migration, invasion metastatic when by cancer cells or their extracellular vesicles. On other hand, tumour-associated glycans recognized C-type lectin receptors possess immunomodulatory which enable growth response evasion. Yet, much remains unknown, concerning mechanisms involved deregulation glycan synthesis how this affects major level. This review summarises findings to date aberrant influence immunity, application spotlights unanswered challenges remaining be solved.

Language: Английский

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Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(11), P. e005548 - e005548

Published: Nov. 1, 2022

Background Next-generation cancer immunotherapies are designed to broaden the therapeutic repertoire by targeting new immune checkpoints including lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin mucin-domain containing-3 (TIM-3). Yet, molecular cellular mechanisms which either receptor functions mediate its inhibitory effects still poorly understood. Similarly, little is known on differential of dual, compared with single, checkpoint inhibition. Methods We here performed in-depth characterization, multicolor flow cytometry, single RNA sequencing multiplex supernatant analysis, using tumor suspensions from patients treated ex vivo novel bispecific antibodies programmed death protein 1 (PD-1) TIM-3 (PD1-TIM3), PD-1 LAG-3 (PD1-LAG3), or anti-PD-1. Results identified patient samples were responsive PD1-TIM3, PD1-LAG3 anti-PD-1 an in vitro approach, validated analysis 659 soluble proteins enrichment for responder signature. found increased abundance activated (HLA-DR + CD25 GranzymeB ) CD8 subset proliferating cells, response antibody treatment. Bispecific antibodies, but not anti-PD-1, significantly a natural killer subset, exhibited tissue-residency Key phenotypic transcriptional changes occurred CXCL13 CD4 all treatments, interleukin-17 secretion signaling toward plasma cells. Interestingly, upregulation was detected as unique pharmacodynamic effect mediated PD1-LAG3, PD1-TIM3 Conclusions Our system reliably assessed responses co-targeting together patients’ infiltrating cells revealed imprinting formats currently tested early clinical trials.

Language: Английский

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Mannose Receptors of Alveolar Macrophages as a Target for the Addressed Delivery of Medicines to the Lungs

Russian Journal of Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 48(1), P. 46 - 75

Published: Feb. 1, 2022

Language: Английский

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