Bone Marrow: The Central Immune System

Schirrmacher, Volker

doi:10.3390/immuno3030019

Cited by 4 publications

(12 citation statements)

References 205 publications

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“…The in-situ ICD-generated EVs and apoptotic bodies are not only useful to load the vaccine IO-VAC R . They also immediately circulate via blood to the BM [4]. There they have the potential to prime cancer-reactive naïve T cells as well as to reactivate pre-existing cancer-reactive memory T cells (MTCs) that reside in distinct niches of the BM.…”

Section: Bone Marrow As a Priming Site For T-cell Responses To Blood-...mentioning

confidence: 99%

“…Twenty years after the original article, new discoveries about the BM have been summarized in a recent review, entitled: Bone marrow: The central immune system (CIS) [4].…”

Section: Bone Marrow As a Priming Site For T-cell Responses To Blood-...mentioning

confidence: 99%

“…These circulate to BM where cancer-reactive T cell responses are primed and boosted. Several such cycles lead to the accumulation of cancer-reactive memory T cells (MTCs), which are maintained in special niches of the BM [4]. They are the basis for long-term systemic anti-cancer immunity [11].…”

Section: Individualized Multimodal Immunotherapy (Imi) As Part Of Fir...mentioning

confidence: 99%

“…Extracellular fluid (lymph) is constantly drained from peripheral tissues through lymphatic vessels into lymph nodes. Thereafter it reaches the bloodstream via the thoracic duct; 75% of the lymph from the entire body is transported through this largest lymphatic vessel [4]. Self-antigens (SAs) transported through blood to the BM and thymus are involved in negative selection of potentially self-reactive B or T cells [4].…”

Section: Bone Marrow: the Central Immune Systemmentioning

confidence: 99%

“…They have been reported to exert profoundly lower side effects in cancer patients than other systemic therapies [3]. Side effects of chemotherapeutics and targeted therapeutics such as small molecule inhibitors often affect the immune system, in particular the important central immune system bone marrow (BM) [4]. They also cause therapy resistances because cancer is heterogenous and capable of developing cell-intrinsic mechanisms to resist cell death and to escape single targeted therapeutics and single targeted immune therapeutics [2].…”

Section: Introductionmentioning

confidence: 99%

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Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution

Schirrmacher,

Van Gool,

Stuecker

2024

Biomedicines

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Oncolytic viruses and combinatorial immunotherapy for cancer (this Special Issue) are both part of cancer treatment at IOZK. This review focusses on an individual multimodal cancer immunotherapy concept developed by IOZK, Cologne, Germany. The scientific rationale for employing three main components is explained: (i) oncolytic Newcastle disease virus, (ii) modulated electrohyperthermia and (iii) individual tumor antigen and oncolytic virus modified dendritic cell vaccine (IO-VACR). The strategy involves repeated cancer-immunity cycles evoked in cancer patients by systemic oncolytic virus exposure plus hyperthermia pretreatment to induce immunogenic cell death followed by intradermal IO-VACR vaccination. As an example of the experience at IOZK, we present the latest results from combining the immunotherapy with standard treatment of patients suffering from glioblastoma multiforme. The promising clinical results in terms of overall survival benefit of additional individualized multimodal immunotherapy are presented. The cancer-immunity cycle, as introduced 10 years ago, describes key important steps occurring locally at the sites of both tumor and draining lymph nodes. This view is extended here towards systemic events occuring in blood where immunogenic cell death-induced tumor antigens are transported into the bone marrow. For 20 years it has been known that bone marrow is an antigen-responsive organ in which dendritic cells present tumor antigens to T cells leading to immunological synapse formation, tumor antigen-specific T cell activation and memory T cell formation. Bone marrow is known to be the most prominent source of de novo cellular generation in the body and to play an important role for the storage and maintenance of immunological memory. Its systemic activation is recommended to augment cancer-immunity cycles.

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Section: Bone Marrow As a Priming Site For T-cell Responses To Blood-...mentioning

confidence: 99%

“…Twenty years after the original article, new discoveries about the BM have been summarized in a recent review, entitled: Bone marrow: The central immune system (CIS) [4].…”

Section: Bone Marrow As a Priming Site For T-cell Responses To Blood-...mentioning

confidence: 99%

Section: Individualized Multimodal Immunotherapy (Imi) As Part Of Fir...mentioning

confidence: 99%

Section: Bone Marrow: the Central Immune Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution

Schirrmacher,

Van Gool,

Stuecker

2024

Biomedicines

Self Cite

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Gemcitabine‐Loaded Injectable Hydrogel for Localized Breast Cancer Immunotherapy

Barough,

Seyfoori,

Askari

et al. 2024

Adv Funct Materials

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Injectable hydrogels for cancer immunotherapy are effective for both active and passive approaches. Tumor‐infiltrating lymphocyte (TIL) immunoshaping can change the tumor microenvironment to favor tumor cell elimination. The primary objective of immunoshaping is to reduce regulatory T‐cells (Tregs), which can enhance the effectiveness of ex vivo immune cell therapy in solid tumors. A shear‐thinning injectable hydrogel that consists of gelatin and Laponite (Gel‐Lap) is used in this study. By optimizing the formulation, their immunotherapeutic and anti‐tumor properties are examined. Gemcitabine (GEM), an anti‐metabolite cancer chemotherapy agent, is loaded into a Gel‐Lap hydrogel (immunogel). The study compares the effects of immunogel on 4T1 inoculated breast cancer animal models. Results show that immunogel increases survival rates and significantly inhibits metastasis. The Treg cell population reduction is observed up to 70% in TILs and splenocyte population in line with CD8+ T‐cells population increment in inguinal lymph nodes near the tumor region; the CD8+ T‐cells function may be mediated through overexpression of eomesodermin (EOMES) as cytotoxic T lymphocyte (CTL) activation transcription factor. The human 3D cell culture model confirmed results in animal data demonstrating T‐cell migration through the hydrogel and anticancer efficacy. Local delivery of GEM using our silicate‐based hydrogel holds promise for editing tumor microenvironment in favor of systemic immune responses.

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Interconnection and Communication between Bone Marrow - The Central Immune System - And the Central Nervous System

Volker

2023

J Neurosci Neurol Disord

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Bone marrow and the central nervous system are both protected by bone. The two systems are interconnected not only structurally but also functionally. In both systems specialized cells communicate through synapses. There exists a tridirectional communication within the neuroimmune network, including the hormonal system, the immune system, and the nervous system. Bone marrow is a priming site for T cell responses to blood-borne antigens including those from the central nervous system. In cases of auto (self) antigens, the responses lead to immune tolerance while in cases of neo (non-self) antigens, the responses lead to neoantigen-specific T cell activation, immune control, and finally to the generation of neoantigen-specific immunological memory. Bone marrow has an important function in the storage and maintenance of immunological memory. It is a multifunctional and very active cell-generating organ, constantly providing hematopoiesis and osteogenesis in finely-tuned homeostasis. Clinical perspectives include mesenchymal stem cell transplantation for tissue repair within the central nervous system.

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Bone Marrow: The Central Immune System

Cited by 4 publications

References 205 publications

Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution

Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution

Gemcitabine‐Loaded Injectable Hydrogel for Localized Breast Cancer Immunotherapy

Interconnection and Communication between Bone Marrow - The Central Immune System - And the Central Nervous System

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