Hematology:

Antibiotic (ABX)-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n = 58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery, n = 40; validation, n = 28). These findings were recapitulated in an immune-competent CAR-T mouse model, in which meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-Ts, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy. This trial was registered at www.clinicaltrials.gov as #NCT06218602.

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Cancer is one of the main public health problems worldwide. Among tumors of the Central Nervous System (CNS), glioblastoma (GBM) affects 49.1% of malignant brain tumors, and despite standard treatment, patients diagnosed with GBM have a dismal prognosis, a high rate of recurrence after tumor resection and poor survival. Since 2016, the World Health Organization (WHO) has included molecular biomarkers in the classification of these tumors, as knowing the heterogeneity and possible genetic changes allows for new therapeutic possibilities. The purpose of this review was to provide an overview of epidemiology and classification, as well as changes in signaling pathways resulting from genetic alterations that affect crucial factors in tumorigenesis, response to treatment and prognosis. Therefore, understanding and characterizing the vast genetic heterogeneity of GBM, both genetic and epigenetic alterations, enable a greater comprehension of the pathogenesis of this tumor, potentially helping to bring new therapeutic approaches and personalization of treatment through the different genetic alterations in each patient.

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Cancer continues to be a major global health burden, with high morbidity and mortality. Building on the success of immune checkpoint inhibitors and adoptive cellular therapy, cancer vaccines have garnered significant interest, but their clinical success remains modest. Benefiting from advancements in technology, many meticulously designed cancer vaccines have shown promise, warranting further investigations to reach their full potential. Cancer vaccines hold unique benefits, particularly for patients resistant to other therapies, and they offer the ability to initiate broad and durable T cell responses. In this review, we highlight the antigen selection for cancer vaccines, introduce the immune responses induced by vaccines, and propose strategies to enhance vaccine immunogenicity. Furthermore, we summarize key features and notable clinical advances of various vaccine platforms. Lastly, we delve into the mechanisms of tumor resistance and explore the potential benefits of combining cancer vaccines with standard treatments and other immunomodulatory approaches to improve vaccine efficacy.

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CONCLUSIONS: CKD significantly exacerbates ischemic muscle pathology in PAD, as evidenced by diminished muscle strength, reduced mitochondrial function, and altered transcriptome profiles. The correlation between uremic toxins and muscle dysfunction suggests that targeting these metabolites may offer therapeutic potential for improving muscle health in PAD patients with CKD.

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Despite novel prophylactic regimens, chronic graft-versus-host disease (cGVHD) remains a challenging complication after allogeneic hematopoietic cell transplantation. cGVHD can affect multiple organs and reduces quality of life, and treatment can cause serious adverse effects. In the past 10 years, the drugs ibrutinib, ruxolitinib, belumosudil, and axatilimab were approved by the US Food and Drug Administration (FDA) for cGVHD. Here, we discuss which signaling pathways and cell types are targeted, the clinical studies that were the basis for FDA approval, and future directions for clinical research.

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In the present era, noncoding RNAs (ncRNAs) have become a subject of considerable scientific interest, with peptides encoded by ncRNAs representing a particularly promising avenue of investigation. The identification of ncRNA-encoded peptides in human cancers is increasing. These peptides regulate cancer progression through multiple molecular mechanisms. Here, we delineate the patterns of diverse ncRNA-encoded peptides and provide a synopsis of the methodologies employed for the identification of ncRNAs that possess the capacity to encode these peptides. Furthermore, we discuss the impacts of ncRNA-encoded peptides on the biological behavior of cancer cells and the underlying molecular mechanisms. In conclusion, we describe the prospects of ncRNA-encoded peptides in cancer and the challenges that need to be overcome.