Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(2), P. 272 - 287.e9

Published: Jan. 26, 2023

Language: Английский

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The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 8, 2023

Interleukin-10 (IL-10) is a pleiotropic cytokine that has fundamental role in modulating inflammation and maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from uncontrolled immune response, mostly through Jak1/Tyk2 STAT3 signaling pathway. On other hand, IL-10 can also have immunostimulating functions under certain conditions. Given pivotal of modulation, this could relevant implications pathologies characterized by hyperinflammatory state, such cancer, or infectious diseases case COVID-19 Post-COVID-19 syndrome. Recent evidence proposed predictor severity mortality for patients with acute post-acute SARS-CoV-2 infection. In context, act endogenous danger signal, released tissues undergoing damage attempt to protect organism harmful hyperinflammation. Pharmacological strategies aimed potentiate restore immunomodulatory action may represent novel promising avenues counteract storm arising hyperinflammation effectively mitigate severe complications. Natural bioactive compounds, derived terrestrial marine photosynthetic organisms able increase expression, useful prevention strategy curb elevation will be discussed here. However, multifaceted nature taken into account attempts modulate its levels.

Language: Английский

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Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 28, 2022

Immunotherapy has become a key therapeutic strategy in the treatment of many cancers. As result, research efforts have been aimed at understanding mechanisms resistance to immunotherapy and how anti-tumor immune response can be therapeutically enhanced. It shown that tumor cell recognition by system plays role effective T targeting therapies patients. One mechanism which cells avoid immunosurveillance is through downregulation Major Histocompatibility Complex I (MHC-I). Downregulation MHC-I described as intrinsic acquired patients with cancer. Depending on mechanism, sometimes restored aid immunity. In this article, we will review current its impact patients, well possible strategies for upregulation MHC-I.

Language: Английский

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Antigen presentation in cancer — mechanisms and clinical implications for immunotherapy

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(9), P. 604 - 623

Published: June 16, 2023

Language: Английский

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Colorectal cancer immunotherapy-Recent progress and future directions

Cancer Letters, Journal Year: 2022, Volume and Issue: 545, P. 215816 - 215816

Published: July 8, 2022

Language: Английский

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Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects

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

Published: Dec. 2, 2023

Abstract The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided immune system with signal to detect eliminate infected or cancerous cells. In context cancer, owing crucial immune-regulatory roles played by MHC-I molecules, abnormal modulation expression function could be hijacked tumor cells escape surveillance attack, thereby promoting tumoral progression impairing efficacy cancer immunotherapy. Here we reviewed discussed recent studies discoveries related their multidirectional functions in development mainly focusing interactions between multiple participators microenvironment highlighting significance targeting for optimizing immunotherapy a deeper understanding dynamic nature functioning mechanism cancer.

Language: Английский

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Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non–Small-Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(11), P. 1311 - 1321

Published: Jan. 11, 2024

PURPOSE Although immune checkpoint inhibitors (ICI) have extended survival in patients with non–small-cell lung cancer (NSCLC), acquired resistance (AR) to ICI frequently develops after an initial benefit. However, the mechanisms of AR NSCLC are largely unknown. METHODS Comprehensive tumor genomic profiling, machine learning–based assessment tumor-infiltrating lymphocytes, multiplexed immunofluorescence, and/or HLA-I immunohistochemistry (IHC) were performed on matched pre- and post-ICI biopsies from treated at Dana-Farber Cancer Institute who developed ICI. Two additional cohorts intervening chemotherapy or targeted therapies between included as controls. RESULTS We comprehensive profiling immunophenotypic characterization samples 82 compared findings a control cohort non-ICI (chemotherapy, N = 32; therapies, 89; both, 17). Putative mutations identified 27.8% immunotherapy-treated cases loss-of-function STK11, B2M, APC, MTOR, KEAP1, JAK1/ 2; these alterations not observed groups. Immunophenotyping demonstrated significant decreases intratumoral CD3e + CD8a T cells, PD-L1–PD1 engagement, well increased distance cells CD8 PD-1 cells. There was decrease HLA class I expression immunotherapy time ( P .005) therapy .01) cohorts. CONCLUSION These highlight heterogeneity NSCLC, which will need be considered when developing novel therapeutic strategies aimed overcoming resistance.

Language: Английский

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Glioblastoma vaccines: past, present, and opportunities

EBioMedicine, Journal Year: 2024, Volume and Issue: 100, P. 104963 - 104963

Published: Jan. 5, 2024

Glioblastoma (GBM) is one of the most lethal central nervous systems (CNS) tumours in adults. As supplements to standard care (SOC), various immunotherapies improve therapeutic effect other cancers. Among them, tumour vaccines can serve as complementary monotherapy or boost clinical efficacy with immunotherapies, such immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapy. Previous studies GBM have suggested that few neoantigens could be targeted due low mutation burden, single-peptide vaccination had limited control monotherapy. Combining diverse antigens, including neoantigens, tumour-associated antigens (TAAs), pathogen-derived optimizing vaccine design strategy may help improvement. In this review, we discussed current platforms, evaluated potential antigenic targets, challenges, perspective opportunities for

Language: Английский

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Precision unveiled: Synergistic genomic landscapes in breast cancer—Integrating single‐cell analysis and decoding drug toxicity for elite prognostication and tailored therapeutics

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(6), P. 3448 - 3472

Published: March 7, 2024

Globally, breast cancer, with diverse subtypes and prognoses, necessitates tailored therapies for enhanced survival rates. A key focus is glutamine metabolism, governed by select genes. This study explored genes associated T cells linked them to metabolism construct a prognostic staging index cancer patients more precise medical treatment.

Language: Английский

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TIGIT is the central player in T-cell suppression associated with CAR T-cell relapse in mantle cell lymphoma

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 26, 2022

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR approved by FDA for MCL. However, development of relapses to recognized poor patient outcomes. Multiple therapies have been other lymphomas resistance mechanisms investigated. underlying relapse MCL not investigated whether any previously reported apply BA-relapsed unknown. Methods To interrogate MCL, we performed single-cell RNA sequencing on 39 longitudinally collected samples from 15 BA-treated patients, multiplex cytokine profiling 80 serial 20 patients. Results We demonstrate that after relapse, proportion T cells, especially cytotoxic cells (CTLs), decreased among non-tumor while myeloid correspondingly increased. TIGIT , LAG3 CD96 were predominant checkpoint molecules expressed exhausted CTLs; was significantly increased relapse. CTLs expanded during remission, then contracted upregulated expression. Tumor also acquired expression leading enhanced interaction tumor monocyte CD155/PVR. In post-relapse HLA-II reduced relative pretreatment remission. Myeloid-derived suppressor (MDSCs) enriched elevated activation markers, including CLU (clusterin) VCAN (versican). Extracellular chemokines (CCL4, CXCL9, CXCL13), soluble inhibitors (sPD-L1, sTIM3, s4-1BB), receptors (sIL-2R, sTNFRII) but Conclusions Our data multiple tumor-intrinsic -extrinsic factors are associated suppression Among these, appears be central player given its cells. The acquisition MCL-specific has T-treated diseases. Together, our suggest co-targeting may prevent thus promote long-term progression-free survival

Language: Английский

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