Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 13, 2023

Abstract In the past period, due to rapid development of next-generation sequencing technology, accumulating evidence has clarified complex role human microbiota in cancer and therapeutic response. More importantly, available seems indicate that modulating composition gut improve efficacy anti-cancer drugs may be feasible. However, intricate complexities exist, a deep comprehensive understanding how interacts with is critical realize its full potential treatment. The purpose this review summarize initial clues on molecular mechanisms regarding mutual effects between development, highlight relationship microbes immunotherapy, chemotherapy, radiation therapy surgery, which provide insights into formulation individualized strategies for management. addition, current emerging microbial interventions as well their clinical applications are summarized. Although many challenges remain now, great importance cannot overstated strategies, it necessary explore holistic approach incorporates modulation cancer.

Язык: Английский

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Targeting the gut microbiota for cancer therapy

Nature reviews. Cancer, Год журнала: 2022, Номер 22(12), С. 703 - 722

Опубликована: Окт. 17, 2022

Язык: Английский

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Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome

Nature Medicine, Год журнала: 2022, Номер 28(11), С. 2344 - 2352

Опубликована: Сен. 22, 2022

Язык: Английский

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Immune effector cell–associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations

Blood, Год журнала: 2023, Номер 142(10), С. 865 - 877

Опубликована: Июнь 10, 2023

Abstract Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, sought build consensus on grading management of immune effector cell–associated hematotoxicity (ICAHT) CAR For this purpose, joint effort between European Society Blood Marrow Transplantation (EBMT) Hematology Association (EHA) involved an international panel 36 experts who met series virtual conferences, culminating 2-day meeting Lille, France. On basis these deliberations, best recommendations were developed. ICAHT, classification system based depth duration neutropenia was developed early (day 0-30) late (after day +30) cytopenia. Detailed risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), diagnostic workup are provided. A further section focuses identifying hemophagocytosis context hematotoxicity. Finally, review evidence provide including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, allogeneic transplantation. conclusion, propose ICAHT as novel category therapy, framework its grading, literature outline expert short- long-term management.

Язык: Английский

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A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy

Nature Medicine, Год журнала: 2023, Номер 29(4), С. 906 - 916

Опубликована: Март 13, 2023

Язык: Английский

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γδ T cells: origin and fate, subsets, diseases and immunotherapy

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Язык: Английский

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An integrated tumor, immune and microbiome atlas of colon cancer

Nature Medicine, Год журнала: 2023, Номер 29(5), С. 1273 - 1286

Опубликована: Май 1, 2023

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification accurate biomarkers clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing tumor matched healthy tissue, complemented whole-genome for further microbiome characterization. A type 1 helper cell, cytotoxic, expression signature, called Immunologic Constant Rejection, captured presence clonally expanded, tumor-enriched clones outperformed conventional prognostic molecular biomarkers, such as consensus subtype microsatellite instability classifications. Quantification genetic immunoediting, defined a lower number neoantigens than expected, refined its value. We identified driven Ruminococcus bromii, associated favorable By combining signature developed validated composite score (mICRoScore), which identifies group excellent survival probability. publicly available dataset provides resource better understanding biology that could facilitate discovery personalized therapeutic approaches.

Язык: Английский

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How I Treat Refractory CRS and ICANS Following CAR T-cell Therapy

Blood, Год журнала: 2023, Номер unknown

Опубликована: Март 29, 2023

The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly due to expanding indications for standard care treatment and the development new investigational products. establishment consensus diagnostic criteria cytokine release syndrome (CRS) immune effector cell associated neurotoxicity (ICANS), alongside steady both tocilizumab corticosteroids treatment, have been essential facilitating widespread use. Pre-emptive interventions prevent more severe toxicities has improved safety, CAR in medically frail populations those at high-risk CRS/ICANS. Nonetheless, persistent or progressive CRS ICANS remains problematic, as it impairs patient outcomes challenging treat. In this case-based discussion, we highlight a series cases and/or refractory front-line interventions. We discuss our approach managing that persist progress beyond initial corticosteroid administration, delineate risk-factors toxicities, emerging anakinra, review mitigation strategies supportive measures improve patients who develop these toxicities.

Язык: Английский

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Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses

Nature Biotechnology, Год журнала: 2023, Номер 42(8), С. 1263 - 1274

Опубликована: Сен. 25, 2023

Язык: Английский

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CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 9, 2022

Abstract Immunotherapy utilizing chimeric antigen receptor T cell (CAR-T) therapy holds promise for hematologic malignancies, however, response rates and associated immune-related adverse effects widely vary among patients. Here we show, by comparing diversity composition of the gut microbiome during different CAR-T therapeutic phases in clinical trial ChiCTR1800017404, that flora characteristically differs patients according to treatment stages, might also reflect patient relapsed/refractory multiple myeloma (MM; n = 43), acute lympholastic leukemia (ALL; 23) non-Hodgkin lymphoma (NHL; 12). We observe significant temporal differences abundance Bifidobacterium, Prevotella, Sutterella, Collinsella between MM complete remission ( 24) those partial 11). Furthermore, find with severe cytokine release syndrome present higher Leuconostoc, Stenotrophomonas, Staphylococcus, which is reproducible an independent cohort 38 This study has important implications understanding biological role responsiveness malignancy patients, may guide intervention increase efficacy. The success rate high blood cancers, yet individual characteristics reduce benefit. show MM, ALL NHL, occurrence are specific alterations.

Язык: Английский

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