Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies DOI Creative Commons
Shizuko Sei, Aysel Ahadova, Derin B. Keskin

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Март 22, 2023

Hereditary cancer syndromes (HCS) account for 5~10% of all diagnosis. Lynch syndrome (LS) is one the most common HCS, caused by germline mutations in DNA mismatch repair (MMR) genes. Even with prospective surveillance, LS associated up to 50% lifetime risk colorectal, endometrial, and other cancers. While significant progress has been made timely identification pathogenic variant carriers monitoring early detection precancerous lesions, cancer-risk reduction strategies are still centered around endoscopic or surgical removal neoplastic lesions susceptible organs. Safe effective prevention critically needed improve life quality longevity HCS carriers. The era precision oncology driven recent technological advances tumor molecular profiling a better understanding genetic factors transformed approaches at-risk individuals, including MMR deficiency leads accumulation insertion deletion microsatellites (MS), which particularly prone polymerase slippage during replication. Mutations coding MS give rise frameshift peptides (FSP) that recognized immune system as neoantigens. Due clonal evolution, tumors share set recurrent predictable FSP neoantigens same different patients. Cancer vaccines composed commonly recurring selected through prediction algorithms have clinically evaluated proven safe immunogenic. Preclinically analogous shown elicit FSP-directed responses exert tumor-preventive efficacy murine models LS. immunopreventive "off-the-shelf" consisting antigens currently investigated clinical trials, feasibility utility personalized individual HLA-restricted epitopes being explored more precise targeting. Here, we discuss immunoprevention approaches, emerging enabling technologies, research gaps, implementation barriers toward translation risk-tailored We will also practicality next-generation based on immunogenic immunoprevention.

Язык: Английский

B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome DOI
Wolf H. Fridman, Maxime Meylan, Florent Petitprez

и другие.

Nature Reviews Clinical Oncology, Год журнала: 2022, Номер 19(7), С. 441 - 457

Опубликована: Апрель 1, 2022

Язык: Английский

Процитировано

398
Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities DOI
Céline M. Laumont, Allyson C. Banville, Mara Gilardi

и другие.

Nature reviews. Cancer, Год журнала: 2022, Номер 22(7), С. 414 - 430

Опубликована: Апрель 7, 2022

Язык: Английский

Процитировано

311
Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers DOI Open Access

Alicia Cristina Peña-Romero,

Esteban Orenes‐Piñero

Cancers, Год журнала: 2022, Номер 14(7), С. 1681 - 1681

Опубликована: Март 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Язык: Английский

Процитировано

149
B cells in the tumor microenvironment: Multi-faceted organizers, regulators, and effectors of anti-tumor immunity DOI Creative Commons
Céline M. Laumont, Brad H. Nelson

Cancer Cell, Год журнала: 2023, Номер 41(3), С. 466 - 489

Опубликована: Март 1, 2023

Язык: Английский

Процитировано

92
Cancer stem cells: advances in knowledge and implications for cancer therapy DOI Creative Commons

Xianjing Chu,

Wentao Tian,

Jiaoyang Ning

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Язык: Английский

Процитировано

85
Immune Microenvironment in Osteosarcoma: Components, Therapeutic Strategies and Clinical Applications DOI Creative Commons
Tianyi Zhu, Jing Han, Yang Liu

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июнь 1, 2022

Osteosarcoma is a primary malignant tumor that tends to threaten children and adolescents, the 5-year event-free survival rate has not improved significantly in past three decades, bringing grief economic burden patients society. To date, genetic background oncogenesis mechanisms of osteosarcoma remain unclear, impeding further research. The immune microenvironment become recent research hot spot, providing novel but valuable insight into heterogeneity multifaceted progression metastasis. However, been vigorously discussed, landscape non-immune component infiltration intensively investigated. Here, we summarize current knowledge classification, features, functions main infiltrating cells, complement system, exosomes microenvironment. In each section, also highlight complex crosstalk network among them corresponding potential therapeutic strategies clinical applications deepen our understanding provide reference for imminent effective therapies with reduced adverse effects.

Язык: Английский

Процитировано

73
Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas DOI
Gabriela Sarti Kinker, Glauco Akelinghton Freire Vitiello, Ariane Barros Diniz

и другие.

Gut, Год журнала: 2023, Номер 72(10), С. 1927 - 1941

Опубликована: Май 25, 2023

To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored relevance T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for generation local antitumour immunity.We characterised functional states spatial organisation PDAC-infiltrating cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling microdissected TLSs, as well in vitro assays. In addition, performed a pan-cancer analysis tumour-infiltrating scRNA-seq sc receptor datasets from eight cancer types. evaluate clinical our findings, used PDAC bulk RNA-seq data The Cancer Genome Atlas PRINCE chemoimmunotherapy trial.We found that subset PDACs harbours fully developed TLSs where proliferate differentiate plasma cells. These mature also support activity are enriched with tumour-reactive Importantly, showed chronically activated, exposed to fibroblast-derived TGF-β may act TLS organisers by producing chemoattractant CXCL13. Identification highly similar subsets clonally expanded CXCL13+ across multiple types further indicated conserved link between tumour-antigen recognition allocation within sheltered hubs tumour microenvironment. Finally, signature reflecting was pretreatment biopsies patients longer survival after receiving different regimens.We provided framework understanding biological role PDAC-associated revealed their potential guide selection future immunotherapy trials.

Язык: Английский

Процитировано

61
Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy DOI Creative Commons
Xufeng Lu, Xiaohong Chen,

Chengyin Lin

и другие.

Advanced Science, Год журнала: 2024, Номер 11(18)

Опубликована: Март 2, 2024

Abstract The induction of cuproptosis, a recently identified form copper‐dependent immunogenic cell death, is promising approach for antitumor therapy. However, sufficient accumulation intracellular copper ions (Cu 2+ ) in tumor cells essential inducing cuproptosis. Herein, an intelligent cuproptosis‐inducing nanosystem constructed by encapsulating oxide (CuO) nanoparticles with the ionophore elesclomol (ES). After uptake cells, ES@CuO degraded to release Cu and ES synergistically trigger thereby significantly inhibiting growth murine B16 melanoma cells. Moreover, further promoted cuproptosis‐mediated immune responses reprogrammed immunosuppressive microenvironment increasing number tumor‐infiltrating lymphocytes secreted inflammatory cytokines. Additionally, combining programmed death‐1 (PD‐1) immunotherapy substantially increased efficacy melanoma. Overall, findings this study can lead use novel strategy therapy, which may enhance checkpoint inhibitor

Язык: Английский

Процитировано

61
Spatial transcriptomics analysis of neoadjuvant cabozantinib and nivolumab in advanced hepatocellular carcinoma identifies independent mechanisms of resistance and recurrence DOI Creative Commons

Shuming Zhang,

Long Yuan, Ludmila Danilova

и другие.

Genome Medicine, Год журнала: 2023, Номер 15(1)

Опубликована: Сен. 18, 2023

Abstract Background Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients. Little is known about the inter- and intra-tumor heterogeneity in cellular signaling networks within HCC tumor microenvironment (TME) that underlie modern systemic therapy. Methods We applied spatial transcriptomics (ST) profiling characterize resection specimens from prospective clinical trial neoadjuvant cabozantinib, multi-tyrosine kinase inhibitor primarily blocks VEGF, nivolumab, PD-1 which 5 out 15 were found pathologic response at time resection. Results ST demonstrated TME responding tumors was enriched immune cells cancer-associated fibroblasts (CAF) pro-inflammatory relative non-responders. The cancer-immune interactions characterized by activation PAX5 module, regulator B cell maturation, colocalized spots increased marker expression suggesting strong activity these cells. HCC-CAF also associated extracellular matrix (ECM) remodeling as there high FOS JUN CAFs adjacent tumor. ECM consistent proliferative fibrosis association immune-mediated regression. Among major responses, single patient experienced early recurrence. analysis this outlier marked heterogeneity, distinctive immune-poor region resembles non-responding across cancer stem markers, potentially mediating escape recurrence patient. Conclusions These data show therapy molecular landscapes provide new targets enhance prolong HCC.

Язык: Английский

Процитировано

51
Cellular interactions in tumor microenvironment during breast cancer progression: new frontiers and implications for novel therapeutics DOI Creative Commons

Tosin Akinsipe,

Rania Mohamedelhassan,

Ayuba Akinpelu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 12, 2024

The breast cancer tumor microenvironment (TME) is dynamic, with various immune and non-immune cells interacting to regulate progression anti-tumor immunity. It now evident that the within TME significantly contribute resistance conventional newly developed therapies. Both in play critical roles onset, uncontrolled proliferation, metastasis, evasion, Consequently, molecular cellular components of have emerged as promising therapeutic targets for developing novel treatments. primarily comprises cells, stromal vasculature, infiltrating cells. Currently, numerous clinical trials targeting specific are underway. However, complexity its impact on evasion immunity necessitate further research develop improved multifaceted nature arises from their phenotypic functional plasticity, which endows them both pro during progression. In this review, we discuss current understanding recent advances anti-tumoral functions implications safe effective therapies control progress.

Язык: Английский

Процитировано

17