Trained immunity: Target for prophylaxis and therapy

Ziogas, Athanasios; Bruno, Mariolina; van der Meel, Roy; Mulder, Willem J.M.; Netea, Mihai G.

doi:10.1016/j.chom.2023.10.015

Cited by 15 publications

(5 citation statements)

References 185 publications

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“…Therapeutic strategies harnessing NK cells with NK-cell engagers should carefully address these hurdles for ongoing research and development and propose alternatives, such as the administration of exogenous NK cells with high cytotoxic potential or the stimulation of memory-like T cells or NK cells, to be as effective as T-cell therapies. The ever-growing knowledge of the “trained immunity” field provides promise for understanding the pivotal epigenetic modifications leading to long-lived memory-like NK cells [ 103 ] and trained myeloid cells [ 104 , 105 ] that could further sustain adaptive and antibody responses to overcome all these challenges.…”

Section: Discussionmentioning

confidence: 99%

Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

Rolin,

Zimmer,

Seguin-Devaux

2024

Cell Mol Immunol

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By binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections. In this review, we discuss how different immune cell types (T and natural killer lymphocytes, as well as myeloid cells) can be bound by immune cell engagers in immunotherapy for cancer and infectious diseases. Furthermore, we explore the preclinical and clinical advancements of these constructs, and we discuss the challenges in translating the current knowledge from cancer to the virology field. Finally, we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.

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Section: Discussionmentioning

confidence: 99%

Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

Rolin,

Zimmer,

Seguin-Devaux

2024

Cell Mol Immunol

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“…BCG is the prototype under this statement, but induction of TI by alternative vaccinations using attenuated agents such as Influenza ( 82 ) or Vaccinia ( 83 ) has also been experimentally demonstrated. Interestingly, not only the active vaccine agent can induce TI, but also some adjuvants included in vaccine formulations can generate this boosted inflammatory response ( 84 ). For instance, the oil-in-water emulsion adjuvant AS03 included in GlaxoSmithKline’s H1/N1 and H5N1 Influenza vaccines ( 85 ), and the lipid nanoparticle carrier employed for mRNA vaccines against COVID-19 ( 86 ).…”

Section: Trained Immunity: Priming To Boost Inflammationmentioning

confidence: 99%

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

López-Collazo,

del Fresno

2024

Front. Immunol.

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For decades, innate immune cells were considered unsophisticated first responders, lacking the adaptive memory of their T and B cell counterparts. However, mounting evidence demonstrates the surprising complexity of innate immunity. Beyond quickly deploying specialized cells and initiating inflammation, two fascinating phenomena – endotoxin tolerance (ET) and trained immunity (TI) – have emerged. ET, characterized by reduced inflammatory response upon repeated exposure, protects against excessive inflammation. Conversely, TI leads to an enhanced response after initial priming, allowing the innate system to mount stronger defences against subsequent challenges. Although seemingly distinct, these phenomena may share underlying mechanisms and functional implications, blurring the lines between them. This review will delve into ET and TI, dissecting their similarities, differences, and the remaining questions that warrant further investigation.

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“…In this work, we hypothesized that exposure to MTB does not only induce an antigen specific T cell response but also impacts the activation state of the innate immune system analogous to the trained immunity phenotype described after BCG vaccination [7]. This hypothesis originated from data we generated in an in vivo model of asymptomatic MTB infection, and from heterologous effects observed in a large clinical cohort [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosisinfection associated immune perturbations correlate with antiretroviral immunity

Tepekule,

Jörimann,

Schenkel

et al. 2023

Preprint

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Infection with Mycobacterium tuberculosis (MTB) remains one of the most important opportunistic infections in people with HIV-1 (PWH). While it is well accepted that active Tuberculosis (TB) leads to rapid progression of immunodeficiency in PWH, the interaction between MTB and HIV-1 during the asymptomatic phase of both infections remains poorly understood. Here, we show in a well-matched cohort of PWH with suppressed HIV-1 viral load that MTB infection is associated with a baseline transcriptional profile away from a Type 1 Interferon towards a proinflammatory cytokine response. The transcriptional changes are conserved during HIV-1 viremia and are inversely correlated with HIV-1 viral load, suggesting that MTB infection-associated perturbations of the innate immune system improve HIV-1 control. In line with these findings, the transcriptional profile of individuals with MTB infection overlaps with that of HIV-1 long term non-progressors. Conversely, during active TB, the transcriptional pattern is reversed, indicating loss of immune control and suggesting a shared immunological mechanism of control and progression for both HIV-1 and MTB infection. In conclusion, our data show that MTB infection is associated with a shift in the activation state of the immune system. This shift contributes to lower HIV-1 viral load in MTB/HIV-1 co-infection and is lost during disease progression.

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Trained immunity: Target for prophylaxis and therapy

Cited by 15 publications

References 185 publications

Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Mycobacterium tuberculosisinfection associated immune perturbations correlate with antiretroviral immunity

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