Macrophage immunotherapy: overcoming impediments to realize promise

Sly, Laura M.; McKay, Derek M.

doi:10.1016/j.it.2022.10.002

Cited by 32 publications

(15 citation statements)

References 58 publications

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“…In contrast, M2 macrophages secrete mainly anti-inflammatory cytokines, such as IL-10 and Arg-1, which play important roles in reducing inflammation and tissue repair [ 57 ]. In the joints of RA patients, macrophages are predominantly polarized to the M1 subtype due to the specific inflammatory milieu, so altering macrophage polarization toward the M2 phenotype is an effective treatment for alleviating RA symptoms [ 58 ]. Moreover, the CS-Cur-TGNCs were able to release Cur at specific inflammatory sites, thus effectively controlling the development of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Chondroitin sulfate-modified tragacanth gum–gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis

Sun,

Du,

Liu

et al. 2024

J Nanobiotechnol

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Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum–gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum–gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Chondroitin sulfate-modified tragacanth gum–gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis

Sun,

Du,

Liu

et al. 2024

J Nanobiotechnol

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“…The therapeutic potential of a defined subpopulation of macrophages has also been explored extensively [ 34 ]. Rybalko et al demonstrated that M1-polarized macrophages could promote muscle functional recovery and inhibit fibrotic tissue deposition [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors

Huo

Zhang

et al. 2023

J Transl Med

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Background Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization. Methods In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms. Results After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity. Conclusions We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.

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“…The platelet secretion of polyphosphate and factor XIIIa cross‐link with fibrin to form a thrombus, thus achieving hemostasis (Scopelliti et al, 2022). The inflammatory process occurs after thrombosis and involves neutrophils (Su & Richmond, 2015), monocytes transformed macrophages (Sly & McKay, 2022), immune cells (T cells, dendritic cells [DCs]) (Caballero‐Sanchez et al, 2022) and some cytokines (Jarczak & Nierhaus, 2022) (chemokines, inflammatory cytokines, growth factors, proteases, etc.) in the inflammatory process of wound healing.…”

Section: Modulation Of Wound Formation and Healingmentioning

confidence: 99%

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Wu,

Liang,

Han

et al. 2023

Journal Cellular Physiology

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The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.

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Macrophage immunotherapy: overcoming impediments to realize promise

Cited by 32 publications

References 58 publications

Chondroitin sulfate-modified tragacanth gum–gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis

Chondroitin sulfate-modified tragacanth gum–gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis

M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

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