bims-traimu Biomed News
on Trained immunity
Issue of 2023‒01‒29
four papers selected by
Yantong Wan
Southern Medical University
  1. Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.
  2. Obesity induces epigenetic memory in innate immune cells.
  3. The role of the microbiota in myelopoiesis during homeostasis and inflammation.
  4. Editorial: Modulation of the immune system by bacteria: From evasion to therapy.
  1. J Immunother Cancer. 2023 Jan;pii: e005518. [Epub ahead of print]11(1):
    Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.
    Jelmer H van Puffelen, Boris Novakovic, Liesbeth van Emst, Denise Kooper, Tahlita C M Zuiverloon, Ursula T H Oldenhof, J Alfred Witjes, Tessel E Galesloot, Alina Vrieling, Katja K H Aben, Lambertus A L M Kiemeney, Egbert Oosterwijk, Mihai G Netea, Joost L Boormans, Antoine G van der Heijden, Leo A B Joosten, Sita H Vermeulen.
      BACKGROUND: BCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.METHODS: The aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine production by peripheral blood mononuclear cells, epigenetic modifications, and changes in the monocyte transcriptome were measured. The frequency of respiratory infections was investigated in two larger cohorts of BCG-treated and non-BCG treated NMIBC patients as a surrogate measurement of trained immunity. Gene-based association analysis of genetic variants in candidate trained immunity genes and their association with recurrence-free survival and progression-free survival after BCG therapy was performed to investigate the hypothesized link between trained immunity and clinical response.
    RESULTS: We found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex vivo stimulation of circulating monocytes 6-12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40 to 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC.
    CONCLUSION: We conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. The data of our gene-based association analysis suggest that a link between trained immunity and oncological outcome may exist. Future studies should further investigate how trained immunity affects the antitumor immune responses in BCG-treated NMIBC patients.
    Keywords:  Cytokines; Genetic Markers; Immunity, Innate; Immunotherapy; Urinary Bladder Neoplasms
    DOI:  https://doi.org/10.1136/jitc-2022-005518
  2. Nat Rev Endocrinol. 2023 Jan 23.
    Obesity induces epigenetic memory in innate immune cells.
    Olivia Tysoe.
      
    DOI:  https://doi.org/10.1038/s41574-023-00806-7
  3. Int Immunol. 2023 Jan 24. pii: dxad002. [Epub ahead of print]
    The role of the microbiota in myelopoiesis during homeostasis and inflammation.
    Yeji Kim, Nobuhiko Kamada.
      The microbiota engages in the development and maintenance of the host immune system. The microbiota affects not only mucosal tissues where it localizes but also the distal organs. Myeloid cells are essential for host defense as first responders of the host immune system. Their generation, called myelopoiesis, is regulated by environmental signals, including commensal microbiota. Hematopoietic stem and progenitor cells in bone marrow can directly or indirectly sense microbiota-derived signals, thereby giving rise to myeloid cell lineages at steady-state and during inflammation. In this review, we discuss the role of commensal microorganisms in the homeostatic regulation of myelopoiesis in the bone marrow. We also outline the effects of microbial signals on myelopoiesis during inflammation and infection, with a particular focus on the development of innate immune memory. Studying the relationship between the microbiota and myelopoiesis will help us understand how the microbiota regulates immune responses at a systemic level beyond the local mucosa.
    Keywords:  Commensal microorganisms; hematopoietic stem and progenitor cells; trained immunity
    DOI:  https://doi.org/10.1093/intimm/dxad002
  4. Front Immunol. 2022 ;13 1112427
    Editorial: Modulation of the immune system by bacteria: From evasion to therapy.
    Marina de Bernard, Maria Kaparakis-Liaskos, Mario Milco D'Elios.
      
    Keywords:  T cells; anti-microbial therapeutics; bacteria elicited trained immunity; bacteria-based therapeutics; bacterial mechanisms
    DOI:  https://doi.org/10.3389/fimmu.2022.1112427
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