☆ 4.6 Review

CAR-T Cell Therapy and the Gut Microbiota

CANCERS (2023)

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Summary: The intestinal microbiota plays a critical role in fermenting dietary fiber into short-chain fatty acids (SCFA), which have various effects on metabolism and immune function. In this study, we investigated the role of the GPR109A receptor in mouse models of allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD). Our findings suggest that GPR109A expression in allo-activated T cells is essential for metabolic homeostasis and expansion, which are necessary for the development of GVHD after allo-HCT.

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Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

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Summary: This study investigated the changes in the intestinal microbiome of patients with B cell lymphoma and leukemia after receiving anti-CD19 CAR T cell therapy, and found that these changes are associated with clinical outcomes.

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Karla A. Lee et al.

Summary: An analysis of metagenomic sequencing of stool samples reveals the association between gut microbiome and response to immune checkpoint blockade therapy in melanoma patients. However, there is limited consistency in the microbiome-based signatures across different populations. Future studies should consider larger sample sizes and examine the complex interplay between clinical factors and the gut microbiome.

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Microbial short-chain fatty acids: a strategy to tune adoptive T cell therapy

Priya Rangan et al.

Summary: The gut microbiota and its metabolites play a crucial role in regulating metabolic, endocrine, and immune functions. The latest research indicates that short-chain fatty acids (SCFAs) produced by the gut microbiota can influence immune functions by regulating gene expression, cell differentiation, and other aspects, particularly affecting T cell phenotypes and functions.

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

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Side-effect management of chimeric antigen receptor (CAR) T-cell therapy

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Summary: CAR T-cell therapy targeting CD19-expressing B cells has shown promising results in treating refractory and/or relapsed B-cell malignancies, but also presents challenges such as cytokine release syndrome and neurotoxicity syndrome. Optimal management strategies for the side-effects associated with CAR T-cell therapy are crucial as it expands into other diseases in hematology and oncology.

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CAR T cells in solid tumors: challenges and opportunities

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Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

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Summary: The study showed that tumor-associated immune and genomic biomarkers of response to combined immune checkpoint blockade (CICB) in melanoma patients were similar to those of monotherapy, while toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Additionally, analysis of gut microbiota revealed a higher abundance of Bacteroides intestinalis in patients experiencing toxicity, along with an upregulation of the inflammatory factor IL-1 beta in colitis samples.

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Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer

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Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma

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Antibiotic Therapy and Low Gut Microbiome Diversity Is Associated with Decreased Response and High Toxicity in BCP-ALL and DLBCL Patients after Treatment with CD19. CAR T-Cells

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CAR T-Cell Associated Neurotoxicity: Mechanisms, Clinicopathologic Correlates, and Future Directions

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JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2019)

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A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Takeshi Tanoue et al.

NATURE (2019)

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Review Biochemistry & Molecular Biology

Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

Romain Villeger et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Multidisciplinary Sciences

Lactose drives Enterococcus expansion to promote graft-versus-host disease

C. K. Stein-Thoeringer et al.

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Article Multidisciplinary Sciences

CXCR1-or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors

Linchun Jin et al.

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Review Hematology

Chimeric Antigen Receptor T Cells: A Race to Revolutionize Cancer Therapy

Marion Subklewe et al.

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